ONCOGENE AND CANCER – FROM BENCH TO CLINIC Edited by Yahwardiah Siregar Oncogene and Cancer – From Bench to Clinic http://dx.doi.org/10.5772/3217 Edited by Yahwardiah Siregar Contributors Daniel Chan, Soo-Chin Lee, Cristina Marchini, Lucia Pietrella, Cristina Kalogris, Chiara Garulli, Federico Gabrielli, Elena Quaglino, Manuela Iezzi, Serenella M. Pupa, Elda Tagliabue, Augusto Amici, Zhongren Zhou, David G. Hick, Erica L. Cain, Alexander Beeser, Yasuko Kitagishi, Mayumi Kobayashi, Satoru Matsuda, Dik-Lung Ma, Victor Pui-Yan Ma, Ka-Ho Leung, Hai-Jing Zhong,Hong-Zhang He, Daniel Shiu-Hin Chan , Chung-Hang Leung, Alexey Stepanenko, Vadym Kavsan, Gabriela Anton, Adriana Plesa, Coralia Bleotu, Anca Botezatu, Mariana Anton, Lorelei Irina Brasoveanu, Mihai Stoian, Takaaki Watanabe, Denisa Ilencikova, Alexandra Kolenova, Yann Estornes, Olivier Micheau, Toufic Renno, Serge Lebecque, Laura Monica Magdalena, Lorand Savu, Ho-Hyung Woo, Setsuko K. Chambers, Gianpiero Di Leva, Michela Garofalo, Wei Liu, James M. Phang, Tiziana Triulzi, Marilena V. Iorio, Elda Tagliabue, Patrizia Casalini, Tetsuo Hirano, Leanna Cheung, Jayne E. Murray, Michelle Haber, Murray D. Norris, Gordana Konjević, Sandra Radenković, Ana Vuletić, Katarina Mirjačić Martinović, Vladimir Jurišić, Tatjana Srdić Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2013 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Viktorija Zgela Typesetting InTech Prepress, Novi Sad Cover InTech Design Team First published January, 2013 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Oncogene and Cancer – From Bench to Clinic, Edited by Yahwardiah Siregar p. cm. ISBN 978-953-51-0858-0 Contents Preface IX Section 1 HER2 Carcinogenesis: Etiology, Treatment and Prevention 1 Chapter 1 Serial Changes in Expression of Proteins in Response to Neoadjuvant Chemotherapy in Breast Cancer 3 Daniel Chan and Soo-Chin Lee Chapter 2 HER2-Driven Carcinogenesis: New Mouse Models for Novel Immunotherapies 39 Cristina Marchini, Lucia Pietrella, Cristina Kalogris, Chiara Garulli, Federico Gabrielli, Elena Quaglino, Manuela Iezzi, Serenella M. Pupa, Elda Tagliabue and Augusto Amici Chapter 3 HER2 Amplification or Overexpression in Upper GI Tract and Breast Cancer with Clinical Diagnosis and Treatment 67 Zhongren Zhou and David G. Hick Section 2 DNA Repair Mechanism and Cancer 91 Chapter 4 Emerging Roles of Atypical Dual Specificity Phosphatases in Cancer 93 Erica L. Cain and Alexander Beeser Chapter 5 DNA Repair Molecules and Cancer Therapeutical Responses 117 Yasuko Kitagishi, Mayumi Kobayashi and Satoru Matsuda Section 3 A New Role of Oncogenes and Tumorsuppressorgenes 129 Chapter 6 Structure-Based Approaches Targeting Oncogene Promoter G-Quadruplexes 131 Dik-Lung Ma, Victor Pui-Yan Ma, Ka-Ho Leung, Hai-Jing Zhong, Hong-Zhang He, Daniel Shiu-Hin Chan and Chung-Hang Leung Chapter 7 Cancer Genes and Chromosome Instability 151 Alexey Stepanenko and Vadym Kavsan VI Contents Chapter 8 Human Papillomaviruses Oncoproteins 183 Gabriela Anton, Adriana Plesa, Coralia Bleotu, Anca Botezatu, Mariana Anton, Lorelei Irina Brasoveanu and Mihai Stoian Section 4 A New Approach on Cancer Mechanism 207 Chapter 9 Model Systems Facilitating an Understanding of Mechanisms for Oncogene Amplification 209 Takaaki Watanabe Chapter 10 MLL Gene Alterations in Acute Myeloid Leukaemia (11q23/MLL+ AML) 225 Denisa Ilencikova and Alexandra Kolenova Chapter 11 Dual Role of TLR3 in Inflammation and Cancer Cell Apoptosis 247 Yann Estornes, Olivier Micheau, Toufic Renno and Serge Lebecque Chapter 12 A Different Approach for Cellular Oncogene Identification Came from Drosophila Genetics 271 Laura Monica Magdalena and Lorand Savu Section 5 Non Coding RNA and Micro RNA in Tumorigenesis 293 Chapter 13 Post-Transcriptional Regulation of Proto-Oncogene c-fms in Breast Cancer 295 Ho-Hyung Woo and Setsuko K. Chambers Chapter 14 Non-Coding RNAs and Cancer 317 Gianpiero Di Leva and Michela Garofalo Chapter 15 MiRNA and Proline Metabolism in Cancer 359 Wei Liu and James M. Phang Chapter 16 microRNA: New Players in Metastatic Process 391 Tiziana Triulzi, Marilena V. Iorio, Elda Tagliabue and Patrizia Casalini Chapter 17 Is CCDC26 a Novel Cancer-Associated Long-Chain Non-Coding RNA? 415 Tetsuo Hirano Section 6 Oncogenes for Transcription Factors 435 Chapter 18 The MYCN Oncogene 437 Leanna Cheung, Jayne E. Murray, Michelle Haber and Murray D. Norris Contents VII Chapter 19 STAT Transcription Factors in Tumor Development and Targeted Therapy of Malignancies 455 Gordana Konjević, Sandra Radenković, Ana Vuletić, Katarina Mirjačić Martinović, Vladimir Jurišić and Tatjana Srdić Preface It took a long journey to really understand what cancer is, although many researcher are still working of finding a definite answer on how to treat cancer, and, what is more important, how to detect cancer very early, when some cells start going abnormal and transform into cancer cells. The immune system might be the best weapon against cancer, since immune defense is programmed to recognize and destroy abnormal cells, but cancer cells may develop many defenses against immune attacks. Advances in biological processes, including apoptosis and cell proliferation, that are known to be dysregulated in tumors need to be understood in molecular mechanisms. During the last decade, scientists have shown an interest to create cancer vaccines as well as DNA vaccines using development of new biotechnological tools to elucidate an immune attack against cancer. Recently, a new players in cancer biology have appeared: microRNAs (miRs or miRNAs), a class of small non-coding RNAs that play important roles in cell differentiation, cell growth and cell death. miRNAs can act either as oncogenes or tumor suppressors and regulate the interaction between cancer cells and the microenvironment. Understanding the function of ncRNAs by focusing on the potential involvement of specific RNA species, such as microRNAs, small nucleolar RNAs, Piwi-interacting RNA, long non-coding RNAs, in the development and progression of cancer is described in this book. The book was written not only for medical students, but it can also be widely used by clinical and biomedical scientists, as well as by doctors studying for their postgraduate research. My thanks are specifically aimed at Intech Open staff (Ms. Reinic, Ms. Blecic, Mr. Greblo and Ms Zgela) who helped finish this book. I would also like to express my thankfulness to all authors who contributed a chapter to this publication. Finally, I hope this book will be useful to the health of mankind worldwide. Yahwardiah Siregar [...]... treatment planning, (2) ER and PR positivity supports use of endocrine therapy regardless of menopausal status in both adjuvant and metastatic disease, and (3) ER and PR receptors are weak prognostic indicators and should not be used to determine whether to treat a patient with adjuvant therapy Newer guidelines from a 8 Oncogene and Cancer – From Bench to Clinic joint panel of the ASCO and the College of American... test (as per ASCO guidelines) is to monitor response to therapy in the metastatic breast cancer setting 6 Candidate Protein Biomarkers with possible clinical application in breast cancer i Topo2-alpha (Topo2) DNA topoisomerase 2-alpha is an enzyme that in humans is encoded by the Topo2 gene This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during... part of extracellular fluid, comprising mostly water (93% by volume) and contains dissolved proteins, glucose, clotting factors, mineral ions, hormones and carbon dioxide Blood plasma is prepared by centrifuging a tube of fresh blood 14 Oncogene and Cancer – From Bench to Clinic containing an anti-coagulant until the blood cells fall to the bottom of the tube The blood plasma is then drawn off In contradistinction,... adsorption to the surface) or specifically (via capture by another antibody specific to the same antigen, in a "sandwich" ELISA) After the antigen is 16 Oncogene and Cancer – From Bench to Clinic immobilized, the detection antibody is added, forming a complex with the antigen The detection antibody can be covalently linked to an enzyme, or can itself be detected by a secondary antibody that is linked to an... clinical trial (121) sought to use serum markers to optimize treatment strategies in breast cancer The authors investigated serum 20 Oncogene and Cancer – From Bench to Clinic Her2 levels (sHer2) in 175 breast cancer patients participating in the GeparQuattro trial This study incorporated neoadjuvant chemotherapy approaches in Her2-positive and negative patients (epirubicin/cyclophosphamide prior to. .. modulation, inflammatory response and protease inhibition (155) In addition, many of the issues associated with massspectrometry- based protein profiling technologies also apply to peptidomics Thus, while this technology looks promising, more confirmatory data is required and awaited 26 Oncogene and Cancer – From Bench to Clinic 3 Cancer- biomarker-family approach The basis for the cancer biomarker family’... associated with increased proliferation and resistance to apoptosis (57) One study analyzed 130 breast carcinomas using IHC analyses for the levels of nuclear and nonnuclear EGFR, and found that 37.7% of the cohort immunostained positively for nuclear EGFR and 6.9% had high levels of expression More importantly, survival analysis 10 Oncogene and Cancer – From Bench to Clinic revealed a significant inverse... confirmed by analysis of independent sample sets, ubiquitin has also been found differentially expressed in breast cancer subtypes by three other studies investigating tissue specimens (73) and cell lines (70, 74) 12 Oncogene and Cancer – From Bench to Clinic iii Predictive markers Several SELDI-TOF MS peaks (not structurally identified) were found indicative of treatment response in breast cancer cell... antibody, and signal intensity proportional to the amount of analyte in the sample spot is generated Signal detection is commonly performed by fluorescence, chemiluminescence or colorimetric methods, and the results are quantified by scanning and analyzed by software such as P-SCAN and ProteinScan RPPA is possibly a useful tool to identify and validate proteins and phospho-proteins in cancer (109,... due to a combination of better detection and lifestyle changes Breast cancer is a disorder influenced by genetic, environmental, behavioral, and reproductive factors The most significant risk factors are gender and age Hereditary forms of breast cancer are often related to mutations in two high-penetrance susceptibility genes namely BRCA-1 and BRCA-2 (1), and account for around 5% of all breast cancer . ONCOGENE AND CANCER – FROM BENCH TO CLINIC Edited by Yahwardiah Siregar Oncogene and Cancer – From Bench to Clinic http://dx.doi.org/10.5772/3217 Edited by Yahwardiah Siregar. www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Oncogene and Cancer – From Bench to Clinic, Edited by Yahwardiah Siregar p. cm. ISBN 978-953-51-0858-0 . should not be used to determine whether to treat a patient with adjuvant therapy. Newer guidelines from a Oncogene and Cancer – From Bench to Clinic 8 joint panel of the ASCO and the College