Bruce Alberts - Molecular Biology of The Cell

I Introduction to the Cell The Evolution of the Cell Introduction From Molecules to the First Cell From Procaryotes to Eucaryotes From Single Cells to Multicellular Organisms References General Cited Small Molecules, Energy, and Biosynthesis Introduction The Chemical Components of a Cell Biological Order and Energy Food and the Derivation of Cellular Energy Biosynthesis and the Creation of Order The Coordination of Catabolism and Biosynthesis References General Cited Macromolecules: Structure, Shape, and Information Introduction Molecular Recognition Processes Nucleic Acids Protein Structure Proteins as Catalysts References General Cited How Cells Are Studied Introduction Looking at the Structure of Cells in the Microscope Isolating Cells and Growing Them in Culture Fractionation of Cells and Analysis of Their Molecules Tracing and Assaying Molecules Inside Cells References General Cited II Molecular Genetics Protein Function Introduction Making Machines Out of Proteins The Birth, Assembly, and Death of Proteins References General Cited Basic Genetic Mechanisms Introduction RNA and Protein Synthesis DNA Repair DNA Replication Genetic Recombination Viruses, Plasmids, and Transposable Genetic Elements References General Cited Recombinant DNA Technology Introduction The Fragmentation, Separation, and Sequencing of DNA Molecules Nucleic Acid Hybridization DNA Cloning DNA Engineering References Cited The Cell Nucleus Introduction Chromosomal DNA and Its Packaging The Global Structure of Chromosomes Chromosome Replication RNA Synthesis and RNA Processing The Organization and Evolution of the Nuclear Genome References Cited Control of Gene Expression Introduction An Overview of Gene Control DNA-binding Motifs in Gene Regulatory Proteins How Genetic Switches Work Chromatin Structure and the Control of Gene Expression The Molecular Genetic Mechanisms That Create Specialized Cell Types Posttranscriptional Controls References General Cited III Internal Organization of the Cell 10 Membrane Structure Introduction The Lipid Bilayer Membrane Proteins References General Cited 11 Membrane Transport of Small Molecules and the Ionic Basis of Membrane Excitability Introduction Principles of Membrane Transport Carrier Proteins and Active Membrane Transport , Ion Channels and Electrical Properties of Membranes References 12 Intracellular Compartments and Protein Sorting Introduction The Compartmentalization of Higher Cells The Transport of Molecules into and out of the Nucleus The Transport of Proteins into Mitochondria and Chloroplasts Peroxisomes The Endoplasmic Reticulum References General Cited 13 Vesicular Traffic in the Secretory and Endocytic Pathways Introduction Transport from the ER Through the Golgi Apparatus Transport from the Trans Golgi Network to Lysosomes Transport from the Plasma Membrane via Endosomes: Endocytosis Transport from the Trans Golgi Network to the Cell Surface: Exocytosis The Molecular Mechanisms of Vesicular Transport and the Maintenance of Compartmental Diversity References General Cited 14 Energy Conversion: Mitochondria and Chloroplasts Introduction The Mitochondrion The Respiratory Chain and ATP Synthase Chloroplasts and Photosynthesis The Evolution of Electron-Transport Chains The Genomes of Mitochondria and Chloroplasts References General Cited 15 Cell Signaling Introduction General Principles of Cell Signaling Signaling via G-Protein-linked Cell-Surface Receptors Signaling via Enzyme-linked Cell-Surface Receptors Target-Cell Adaptation The Logic of Intracellular Signaling: Lessons from Computer-based "Neural Networks" References General Cited 16 The Cytoskeleton Introduction The Nature of the Cytoskeleton Intermediate Filaments Microtubules Cilia and Centrioles Actin Filaments Actin-binding Proteins Muscle References General Cited 17 The Cell-Division Cycle Introduction The General Strategy of the Cell Cycle The Early Embryonic Cell Cycle and the Role of MPF Yeasts and the Molecular Genetics of Cell-Cycle Control Cell-Division Controls in Multicellular Animals References General Cited 18 The Mechanics of Cell Division Introduction An Overview of M Phase Mitosis Cytokinesis References General Cited IV Cells in Their Social Context 19 Cell Junctions, Cell Adhesion, and the Extracellular Matrix Introduction Cell Junctions Cell-Cell Adhesion The Extracellular Matrix of Animals Extracellular Matrix Receptors on Animal Cells: The Integrins The Plant Cell Wall References Cited 20 Germ Cells and Fertilization Introduction The Benefits of Sex Meiosis Eggs Sperm Fertilization References General Cited 21 Cellular Mechanisms of Development Introduction Morphogenetic Movements and the Shaping of the Body Plan Cell Diversification in the Early Animal Embryo , Cell Memory, Cell Determination, and the Concept of Positional Values The Nematode Worm: Developmental Control Genes and the Rules of Cell Behavior Drosophila and the Molecular Genetics of Pattern Formation I Genesis of the Body Plan Drosophila and the Molecular Genetics of Pattern Formation II Homeotic Selector Genes and the Patterning of Body Parts , Plant Development Neural Development References General Cited 22 Differentiated Cells and the Maintenance of Tissues Introduction Maintenance of the Differentiated State Tissues with Permanent Cells Renewal by Simple Duplication Renewal by Stem Cells: Epidermis , Renewal by Pluripotent Stem Cells: Blood Cell Formation , Genesis, Modulation, and Regeneration of Skeletal Muscle Fibroblasts and Their Transformations: The Connective-Tissue Cell Family Appendix References General Cited 23 The Immune System Introduction The Cellular Basis of Immunity The Functional Properties of Antibodies The Fine Structure of Antibodies The Generation of Antibody Diversity T Cell Receptors and Subclasses MHC Molecules and Antigen Presentation to T Cells Cytotoxic T Cells Helper T Cells and T Cell Activation Selection of the T Cell Repertoire References General Cited 24 Cancer Introduction Cancer as a Microevolutionary Process The Molecular Genetics of Cancer References General Cited I Introduction to the Cell Part I Introduction to the Cell The Evolution of the Cell Part I Introduction to the Cell Chapter The Evolution of the Cell Introduction All living creatures are made of cells - small membrane-bounded compartments filled with a concentrated aqueous solution of chemicals The simplest forms of life are solitary cells that propagate by dividing in two Higher organisms, such as ourselves, are like cellular cities in which groups of cells perform specialized functions and are linked by intricate systems of communication Cells occupy a halfway point in the scale of biological complexity We study them to learn, on the one hand, how they are made from molecules and, on the other, how they cooperate to make an organism as complex as a human being All organisms, and all of the cells that constitute them, are believed to have descended from a common ancestor cell through evolution by natural selection This involves two essential processes: (1) the occurrence of random variation in the genetic information passed from an individual to its descendants and (2) selection in favor of genetic information that helps its possessors to survive and propagate Evolution is the central principle of biology, helping us to make sense of the bewildering variety in the living world This chapter, like the book as a whole, is concerned with the progression from molecules to multicellular organisms It discusses the evolution of the cell, first as a living unit constructed from smaller parts and then as a building block for larger structures Through evolution, we introduce the cell components and activities that are to be treated in detail, in broadly similar sequence, in the chapters that follow Beginning with the origins of the first cell on earth, we consider how the properties of certain types of large molecules allow hereditary information to be transmitted and expressed and permit evolution to occur Enclosed in a membrane, these molecules provide the essentials of a self-replicating cell Following this, we describe the major transition that occurred in the course of evolution, from small bacteriumlike cells to much larger and more complex cells such as are found in present-day plants and animals Lastly, we suggest ways in which single free-living cells might have given rise to large multicellular organisms, becoming specialized and cooperating in the formation of such intricate organs as the brain Clearly, there are dangers in introducing the cell through its evolution: the large gaps in our knowledge can be filled only by speculations that are liable to be wrong in many details We cannot go back in time to witness the unique molecular events that took place billions of years ago But those ancient events have left many traces for us to analyze Ancestral plants, animals, and even bacteria are preserved as fossils Even more important, every modern organism provides evidence of the character of living organisms in the past Present-day biological molecules, in particular, are a rich source of information about the course of evolution, revealing fundamental similarities between the most disparate of living organisms and allowing us to map out the differences between them on an objective universal scale These molecular similarities and differences present us with a problem like that which confronts the literary scholar who seeks to establish the original text of an ancient author by comparing a mass of variant manuscripts that have been corrupted through repeated copying and editing The task is hard, and the evidence is incomplete, but it is possible at least to make intelligent guesses about the major stages in the evolution of living cells Part I Introduction to the Cell Chapter The Evolution of the Cell From Molecules to the First Cell1 Simple Biological Molecules Can Form Under Prebiotic Conditions1, The conditions that existed on the earth in its first billion years are still a matter of dispute Was the surface initially molten? Did the atmosphere contain ammonia, or methane? Everyone seems to agree, however, that the earth was a violent place with volcanic eruptions, lightning, and torrential rains There was little if any free oxygen and no layer of ozone to absorb the ultraviolet radiation from the sun The radiation, by its photochemical action, may have helped to keep the atmosphere rich in reactive molecules and far from chemical equilibrium Simple organic molecules (that is, molecules containing carbon) are likely to have been produced under such conditions The best evidence for this comes from laboratory experiments If mixtures of gases such as CO2, CH4, NH3, and H2 are heated with water and energized by electrical discharge or by ultraviolet radiation, they react to form small organic molecules - usually a rather small selection, each made in large amounts (Figure 1-1) Among these products are compounds, such as hydrogen cyanide (HCN) and formaldehyde (HCHO), that readily undergo further reactions in aqueous solution (Figure 1-2) Most important, representatives of most of the major classes of small organic molecules found in cells are generated, including amino acids, sugars, and the purines and pyrimidines required to make nucleotides Although such experiments cannot reproduce the early conditions on the earth exactly, they make it plain that the formation of organic molecules is surprisingly easy And the developing earth had immense advantages over any human experimenter; it was very large and could produce a wide spectrum of conditions But above all, it had much more time - tens to hundreds of millions of years In such circumstances it seems very likely that, at some time and place, many of the simple organic molecules found in present-day cells accumulated in high concentrations Complex Chemical Systems Can Develop in an Environment That Is Far from Chemical Equilibrium Simple organic molecules such as amino acids and nucleotides can associate to form polymers One amino acid can join with another by forming a peptide bond, and two nucleotides can join together by a phosphodiester bond The repetition of these reactions leads to linear polymers known as polypeptides and polynucleotides, respectively In present-day living cells, large polypeptides - known as proteins - and polynucleotides - in the form of both ribonucleic acids (RNA) and deoxyribonucleic acids (DNA)are commonly viewed as the most important constituents A restricted set of 20 amino acids constitute the universal building blocks of the proteins, while RNA and DNA molecules are constructed from just four types of nucleotides each Although it is uncertain why these particular sets of monomers were selected for biosynthesis in preference to others that are chemically similar, we shall see that the chemical properties of the corresponding polymers suit them especially well for their specific roles in the cell The earliest polymers may have formed in any of several ways - for example, by the heating of dry organic compounds or by the catalytic activity of high concentrations of inorganic polyphosphates or other crude mineral catalysts Under laboratory conditions the products of similar reactions are polymers of variable length and random sequence in which the particular amino acid or nucleotide added at any point depends mainly on chance (Figure 1-3) Once a polymer has formed, however, it can itself influence subsequent chemical reactions by acting as a catalyst The origin of life requires that in an assortment of such molecules there must have been some possessing, if only to a small extent, a crucial property: the ability to catalyze reactions that lead, directly or indirectly, to production of more molecules of the catalyst itself Production of catalysts with this special self-promoting property would be favored, and the molecules most efficient in aiding their own production would divert raw materials from the production of other substances In this way one can envisage the gradual development of an increasingly complex chemical system of organic monomers and polymers that function together to generate more molecules of the same types, fueled by a supply of simple raw materials in the environment Such an autocatalytic system would have some of the properties we think of as characteristic of living matter: it would comprise a far from random selection of interacting molecules; it would tend to reproduce itself; it would compete with other systems dependent on the same feedstocks; and if deprived of its feedstocks or maintained at a wrong temperature that upsets the balance of reaction rates, it would decay toward chemical equilibrium and "die." But what molecules could have had such autocatalytic properties? In present-day living cells the most versatile catalysts are polypeptides, composed of many different amino acids with chemically diverse side chains and, consequently, able to adopt diverse three-dimensional forms that bristle with reactive sites But although polypeptides are versatile as catalysts, there is no known way in which one such molecule can reproduce itself by directly specifying the formation of another of precisely the same sequence Polynucleotides Are Capable of Directing Their Own Synthesis3 Polynucleotides have properties that contrast with those of polypeptides They have more limited capabilities as catalysts, but they can directly guide the formation of exact copies of their own sequence This capacity depends on complementary pairing of nucleotide subunits, which enables one polynucleotide to act as a template for the formation of another In the simplest case a polymer composed of one nucleotide (for example, polycytidylic acid, or poly C) can line up the subunits required to make another polynucleotide (in this example, polyguanylic acid, or poly G) along its surface, thereby promoting their polymerization into poly G (Figure 1-4) Because C subunits preferentially bind G subunits, and vice versa, the poly-G molecule in turn can Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Table 24-3 Some Changes Commonly Observed When a Normal Tissue-Culture Cell Is Transformed by a Tumor Virus Plasma-membrane-related abnormalities A Enhanced transport of metabolites B Excessive blebbing of plasma membrane C Increased mobility of plasma membrane proteins Adherence abnormalities A Diminished adhesion to surfaces; therefore able to maintain a rounded morphology B Failure of actin filaments to organize into stress fibers C Reduced external coat of fibronectin D High production of plasminogen activator, causing increased Growth and division abnormalities A Growth to an unusually high cell density B Lowered requirement for growth factors C Less anchorage dependence (can grow even without attachment to rigid surface) D 'Immortal' (can continue proliferating indefinitely) E Can cause tumors when injected into susceptible animals Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-22 Cell transformation by the Rous sarcoma virus The scanning electron micrographs show cells in culture infected with a form of the Rous sarcoma virus that carries a temperature-sensitive mutation in the gene responsible for transformation (the v- src oncogene) (A) The cells are transformed and have an abnormal rounded shape at low temperature (34°C), where the oncogene product is functional (B) The same cells adhere strongly to the culture dish and thereby regain their normal flattened appearance when the oncogene product is inactivated by a shift to higher temperature (39°C) (Courtesy of G Steven Martin.) Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-23 The structure of the Rous sarcoma virus (A) The organization of the viral genome as compared with that of a more typical retrovirus (murine leukemia virus) Rous sarcoma virus is unusual among the retroviruses that carry oncogenes in that it has retained all the three viral genes required for the ordinary viral life cycle: gag (which produces a polyprotein that is cleaved to generate the capsid proteins), pol (which produces reverse transcriptase and an enzyme involved in integrating the viral chromosome into the host genome), and env (which produces the envelope glycoprotein) In other oncogenic retroviruses one or more of these viral genes are wholly or partly lost in exchange for the acquisition of the transforming oncogene, and therefore infectious particles of the transforming virus can be generated only in a cell that is simultaneously infected with a nondefective, nontransforming helper virus, which supplies the missing functions (Often the transforming oncogene is fused to a residual fragment of gag, leading to production of a hybrid oncogenic protein that includes part of the Gag sequence.) (B) The relationship between the v- src oncogene and the cellular src proto-oncogene from which it has been derived The introns present in cellular src have been spliced out of v- src;in addition, v- src contains mutations that alter the amino acid sequence of the protein, making it hyperactive and unregulated as a tyrosine-specific protein kinase Rous sarcoma virus has been highly selected (by cancer research workers) for its ability to transform cells to neoplasia, and it does this with unusual speed and efficiency Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Table 24-4 Some Oncogenes Originally Identified Through Their Presence in Transforming Retroviruses Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-24 Insertional mutagenesis In this example the process activates a gene called Wnt-1 (formerly called int-1) and produces breast cancer in mice infected with the mouse mammary tumor virus (MMTV) The sites of MMTV integration observed in 19 different tumor isolates are indicated by arrows Note that the insertions can activate transcription of the Wnt-1 gene from distances of more than 10,000 nucleotide pairs away and from either side of the gene This effect is attributed to a powerful enhancer DNA sequence present in the terminal repeats of the MMTV genome Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Table 24-5 Some Oncogenes Originally Identified by Means Other Than Their Presence in Transforming Retroviruses Means of Detection Oncogenes Insertional mutation Amplification Transfection Translocation Wnt-1 (int-1), fgf-3 (int-2), Notch-1 (int-3), lck L- myc, N- myc neu, N- ras, trk, ret bcl-2, RARa Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-25 The conversion of the abl proto-oncogene into an oncogene in patients with chronic myelogenous leukemia The chromosome translocation responsible joins the bcr gene on chromosome 22 to the abl gene from chromosome 9, thereby generating a Philadelphia chromosome (see Figure 24-4) The resulting fusion protein has the amino terminus of the Bcr protein joined to the carboxyl terminus of the Abl tyrosine protein kinase In consequence, the Abl kinase domain presumably becomes inappropriately active, driving excessive proliferation of a clone of hemopoietic cells in the bone marrow Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-26 The activities and cellular locations of the products of the main classes of known proto-oncogenes Some representative proto-oncogenes in each class are indicated in brackets Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-27 Three ways in which a proto-oncogene can be converted into an oncogene A fourth mechanism (not shown) involves recombination between retroviral DNA and a proto-oncogene (see Figure 24-24) This has effects similar to those of chromosome rearrangement, bringing the proto-oncogene under the control of a viral enhancer and/or fusing it to a viral gene that is actively transcribed Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-34 How replication of damaged DNA can lead to chromosome abnormalities and gene amplification The diagram shows one of several possible mechanisms The process begins with accidental DNA damage in a cell that lacks functional p53 protein Instead of halting at the p53-dependent checkpoint in the G1 phase of the division cycle, where a normal cell with damaged DNA would halt until the damage was repaired, the p53-defective cell enters S phase, with the consequences shown Once a chromosome carrying a duplication and lacking a telomere has been generated, repeated rounds of replication, chromatid fusion, and unequal breakage can increase the number of copies of the duplicated region still further Selection in favor of cells with increased numbers of copies of a gene in the affected chromosomal region will thus lead to mutants in which the gene is amplified to a high copy number The multiple copies may eventually become visible as a homogeneously staining region in the chromosome, or they may - either through a recombination event or through unrepaired DNA strand breakage become excised from their original locus and so appear as independent double minute chromosomes (see Figure 24-2020) Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-28 Oncogene collaboration in transgenic mice The graphs show the incidence of tumors in three types of transgenic mice, one carrying a myc oncogene, one carrying a ras oncogene, and one carrying both oncogenes For these experiments two lines of transgenic mice were first constructed One carries an inserted copy of an oncogene created by fusing the proto-oncogene myc with the mouse mammary tumor virus promoter/enhancer (which then drives myc overexpression in specific tissues such as the mammary gland) The other line carries an inserted copy of the oncogene v-H- rasunder control of the same promoter/enhancer Both strains of mice develop tumors much more frequently than normal, most often in the mammary or salivary glands Mice that carry both oncogenes together were obtained by crossing the two strains These hybrids develop tumors at a far higher rate still, much greater than the sum of the rates for the two oncogenes separately Nevertheless, the tumors arise only after a delay and only from a small proportion of the cells in the tissues where the two genes are expressed Some further accidental change, in addition to the two oncogenes, is apparently required for the development of cancer (After E Sinn et al., Cell 49:465-475, 1987 © Cell Press.) Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-29 The genetic mechanisms underlying retinoblastoma In the hereditary form all cells in the body lack one of the normal two functional copies of a tumor suppressor gene, and tumors occur where the remaining copy is lost or inactivated by a somatic mutation In the nonhereditary form all cells initially contain two functional copies of the gene, and the tumor arises because both copies are lost or inactivated through the coincidence of two somatic mutations in one cell Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-30 Six ways of losing the remaining good copy of a tumor suppressor gene A cell that is defective in only one of its two copies of a tumor suppressor gene usually behaves as a normal, healthy cell; the diagrams show how it may come to lose the function of the other gene copy as well and thereby progress toward cancer Cloned DNA probes can be used in conjunction with restriction-fragment length polymorphisms (see Chapter 7) to analyze the tumor DNA and so to discover which type of event has occurred in a given patient Note that most of the mechanisms result in a cell that totally lacks either the maternal or the paternal copy of the tumor suppressor gene, along with adjacent chromosomal regions This is reflected in a loss of heterozygosity in the neighborhood of the genetic defect Loss of heterozygosity at a specific site in the genome is a hallmark of a cancer dependent on loss of the function of a tumor suppressor gene (After W.K Cavenee et al., Nature 305:779-784, 1983 © 1983 Macmillan Magazines Ltd.) Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Table 24-6 Viruses Associated with Human Cancers Virus DNA viruses Papovavirus family Papillomavirus (many distinct strains) carcinoma of uterine cervix Hepadnavirus family Hepatitis-B virus Herpesvirus family Epstein-Barr virus nasopharyngeal carcinoma RNA viruses Retrovirus family Human T-cell leukemia virus type I (HTLV-I) Human immunodeficiency virus (HIV-1, the AIDS virus) Associated Tumors Areas of High Incidence warts (benign) worldwide worldwide liver cancer (hepatocellular carcinoma) Southeast Asia, tropical Africa Burkitt's lymphoma (cancer of B lymphocytes) Southern China, Greenland (Inuit) West Africa, Papua New Guinea adult T-cell leukemia/lymphoma Kaposi's sarcoma [cancer of endothelial cells of blood vessels or lymphatics (?)] Japan (Kyushu), West Indies Central Africa For all the above viruses, the number of people infected is much larger than the number who develop cancer: the viruses must act in conjunction with other factors Moreover, some of the viruses probably contribute to cancer only indirectly; for example, HIV-1, by obliterating cell-mediated immune defenses, may allow endothelial cells transformed by some other agent to thrive as a tumor instead of being destroyed by the immune system Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-31 The SV40 virus The structure of the capsid of this widely studied DNA virus that infects monkeys has been determined by x-ray diffraction (Courtesy of Robert Grant, Stephen Crainic, and James M Hogle.) Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-32 How certain papillomaviruses are thought to give rise to cancer of the uterine cervix Papillomaviruses have double-stranded circular DNA chromosomes of about 8000 nucleotide pairs In a wart or other benign infection these chromosomes are stably maintained in the basal cells of the epithelium as plasmids whose replication is regulated so as to keep step with the chromosomes of the host (left) Rare accidents can cause the integration of a fragment of such a plasmid into a chromosome of the host, altering the environment of the viral genes and disrupting the control of their expression The consequent unregulated production of viral replication proteins - in particular, the products of the viral E6 and E7 genes - tends to drive the host cell into S phase, thereby helping to generate a cancer (right) Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-33 Activation of cell proliferation by the SV40 DNA tumor virus SV40 uses a single dual-purpose viral protein, called large T antigen, to sequester both Rb and p53; other related DNA tumor viruses use two separate viral proteins (E6 and E7 in the case of papillomavirus) for the same purpose Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-35 Cross-section of an adenomatous polyp from the colon The polyp protrudes into the lumen of the colon The rest of the wall of the colon is covered with normal colonic epithelium, forming typical short glands; the epithelium on the polyp appears mildly abnormal, forming longer glands (Courtesy of Anne Campbell.) Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Table 24-7 Permission to reproduce this table in this web version of Molecular Biology of the Cell is either pending or has not been granted Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-36 Typical sequence of genetic changes underlying the development of a colorectal carcinoma Note that the loss of APC, DCC,or p53 generally requires two mutations, to eliminate both copies of the gene Thus the changes shown here correspond to a total of seven mutations (After E.R Fearon and B Vogelstein, Cell 61:759-767, 1990.) Part IV Cells in Their Social Context Chapter 24 Cancer The Molecular Genetics of Cancer 15 Figure 24-37 Each tumor will generally contain a different set of genetic lesions In this schematic diagram, W, X, Y, and Z denote alterations in as yet undiscovered tumor suppressor genes or oncogenes Tumors that arise from different tissues are generally more different in their genetic abnormalities than tumors of similar origin Part IV Cells in Their Social Context Chapter 24 Cancer References General Brugge, J.; Curran, T.; Harlow, E.; McCormick, F., eds Origins of Human Cancer Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press, 1991 Cairns, J Cancer: Science and Society San Francisco: W.H Freeman, 1978 Cancer Biology: Readings from Scientific American New York: W.H Freeman, 1986 De Vita, V.T.; Hellman, S.; Rosenberg, S.A., eds Cancer: Principles and Practice of Oncology, 4th ed Philadelphia: Lippincott, 1993 Franks, L.M.; Teich, N.M., eds Introduction to the Cellular and Molecular Biology of Cancer, 2nd ed Oxford, UK: Oxford University Press, 1991 Varmus, H.; 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Cited IV Cells in Their Social Context 19 Cell Junctions, Cell Adhesion, and the Extracellular Matrix Introduction Cell Junctions Cell- Cell Adhesion The Extracellular Matrix of Animals Extracellular... line of primitive cells that evolved the mechanism of protein synthesis Membranes Defined the First Cell7 One of the crucial events leading to the formation of the first cell must have been the