CARCINOGENESIS Edited by Kathryn Tonissen Carcinogenesis http://dx.doi.org/10.5772/2982 Edited by Kathryn Tonissen Contributors Francesca Duraturo, Raffaella Liccardo, Angela Cavallo, Marina De Rosa, Paola Izzo, Maria Auxiliadora Vieira do Carmo, Patrícia Carlos Caldeira, Andrés Castillo, Anna Ptak, Ewa Lucja Gregoraszczuk, Ming-Chei Maa, Tzeng-Horng Leu, Ewa Balcerczak, Aleksandra Sałagacka, Malwina Bartczak-Tomczyk, Marek Mirowski, Maneet Bhatia, Therese C. Karlenius, Giovanna Di Trapani, Kathryn F. Tonissen, Hiroko Kuwabara, Masahiko Yoneda, Zenzo Isogai, M.E. Hernández-Caballero, Jinhui Zhang, Lei Wang, Yong Zhang, Junxuan Lü, Naoki Ashizawa, Takeo Shimo, Magdy Sayed Aly, Amani Abd ElHamid Mahmoud, Pornngarm Limtrakul, Pornsiri Pitchakarn, Shugo Suzuki, Mohamed F. El-Refaei, Essam A. Mady 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 Oliver Kurelic 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 Carcinogenesis, Edited by Kathryn Tonissen p. cm. ISBN 978-953-51-0945-7 Contents Preface IX Section 1 Cancer Pre-Disposition and Pre-Cancerous Risk Classification 1 Chapter 1 Synergistic Effects of Low-Risk Variant Alleles in Cancer Predisposition 3 Francesca Duraturo, Raffaella Liccardo, Angela Cavallo, Marina De Rosa and Paola Izzo Chapter 2 Binary System of Grading Epithelial Dysplasia in Oral Leukoplakias 25 Maria Auxiliadora Vieira do Carmo and Patrícia Carlos Caldeira Section 2 Cancer Development and Progression 43 Chapter 3 Human Papillomavirus and Carcinogenesis in the Upper Aero-Digestive Tract 45 Andrés Castillo Chapter 4 Oestrogens, Xenoestrogens and Hormone-Dependent Cancers 63 Anna Ptak and Ewa Lucja Gregoraszczuk Chapter 5 EPS8, an Adaptor Protein Acts as an Oncoprotein in Human Cancer 87 Ming-Chei Maa and Tzeng-Horng Leu Chapter 6 FJ194940.1 Gene and Its Protein Product ACJ04040.1 – Potential Tumor Marker – From Protein to cDNA and Chromosomal Localization 105 Ewa Balcerczak, Aleksandra Sałagacka, Malwina Bartczak-Tomczyk and Marek Mirowski VI Contents Chapter 7 The Interaction Between Redox and Hypoxic Signalling Pathways in the Dynamic Oxygen Environment of Cancer Cells 125 Maneet Bhatia, Therese C. Karlenius, Giovanna Di Trapani and Kathryn F. Tonissen Chapter 8 Expressional Alterations of Versican, Hyaluronan and Microfibril Associated Proteins in the Cancer Microenvironment 153 Hiroko Kuwabara, Masahiko Yoneda and Zenzo Isogai Chapter 9 Molecular Mechanisms of Metastasis: Epithelial-Mesenchymal Transition, Anoikis and Loss of Adhesion 165 M.E. Hernández-Caballero Section 3 Animal Model Systems to Study Carcinogenesis 195 Chapter 10 Lobe-Specific Carcinogenesis in the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) Mouse Model 197 Jinhui Zhang, Lei Wang, Yong Zhang and Junxuan Lü Chapter 11 Mechanism of Urinary Bladder Carcinogenesis Induced by a Xanthine Oxidoreductase Inhibitor, in Rats 221 Naoki Ashizawa and Takeo Shimo Section 4 Natural Products that Prevent or Treat Cancer 237 Chapter 12 Cancer Chemoprevention by Dietary Polyphenols 239 Magdy Sayed Aly and Amani Abd ElHamid Mahmoud Chapter 13 Kuguacin J, a Triterpenoid from Momordica charantia Linn: A Comprehensive Review of Anticarcinogenic Properties 275 Pornngarm Limtrakul, Pornsiri Pitchakarn and Shugo Suzuki Chapter 14 Regulation of Apoptosis, Invasion and Angiogenesis of Tumor Cells by Caffeic Acid Phenethyl Ester 297 Mohamed F. El-Refaei and Essam A. Mady Preface An increased understanding of the molecular, biochemical and cellular processes governing carcinogenesis can only be of benefit in improving the effectiveness of strategies used to prevent and treat cancer. Since cancer is a multifaceted and complex disease a number of factors can contribute to its development and progression. A broad knowledge of these factors may aid in understanding how they interact and influence the processes of initiating and promoting cancer. This in turn enables more effective preventative and therapeutic strategies to be devised and more relevant prognostic tools to be developed. This book includes comprehensive reviews and some specialized experimental findings that cover diverse processes that contribute to carcinogenesis, its diagnosis and treatment. The goal is for these examples to inform and influence a reader’s own specialty by stimulating thinking across a diverse range of topics. A cross fertilization of ideas arising from understanding the various preventative, diagnostic and therapeutic approaches together with a broad knowledge of factors that affect cancer progression could be the impetus for further progress in tackling a disease that still exerts a heavy human toll worldwide. Section 1 includes genetic, molecular and morphological approaches to assessing cancer susceptibility and classifying the risk of developing a cancer. While individual mutations are known to influence cancer formation a knowledge of the synergistic effects of low-risk variant alleles are also important when assessing predisposition to cancer. This section also describes a binary system using morphology and molecular analysis for classifying pre-cancerous lesions into either high or low-risk potential to subsequently develop into oral carcinoma. Section 2 contains chapters that discuss the various mechanisms and stimuli that may contribute to the initiation of cancer or influence progression of the disease into a metastatic state. These stimuli include infection by the human papillomavirus and hormonal stimuli such as oestrogens. Specific proteins may also play a role in carcinogenesis and therefore have prognostic or therapeutic value. Examples of oncogenes and tumor markers, along with their characterisation in cancer cells, are described in this book. The oxygen environment of a cancer cell is an important determinant of carcinogenesis and a description of the redox and hypoxic signaling pathways and how they influence cancer development and metastasis is provided. The cancer microenvironment also plays a role in cancer progression and is the focus X Preface of a chapter that assesses the expression of specific stromal proteins in cancer tissues. Metastasis involves the movement of tumor cells to a distant tissue and the process of epithelial-mesenchymal transition (EMT) is described in detail in the final chapter of this section. The study of cancer and how it develops, progresses and responds to treatments or chemopreventive agents is often conducted in animal models. Section 3 contains chapters that describe specialized models for studying cancers and offer key insights into interpreting and adapting animal studies into human consequences. Natural products are increasingly becoming recognised as an important tool for both preventing and treating cancer. Section 4 contains chapters describing naturally sourced compounds, including dietary polyphenols, and their characterisation as chemopreventive or therapeutic agents. This book is aimed towards researchers, students and medical practitioners wishing to obtain knowledge of the processes that underpin the broader carcinogenesis field. The goal is to inspire new ideas and innovative research directions, so that ultimately cancer will be defeated. The contributions by each of the specialist authors for their chapters and by Professor Krystyna Frenkel for the initial concept and reviews, together with the assistance from the extremely professional staff at InTech is greatly valued and appreciated in preparing this book. Associate Professor Kathryn Tonissen School of Biomolecular and Physical Sciences and Eskitis Institute for Cell and Molecular Therapies Griffith University Nathan, Qld Brisbane Australia . CARCINOGENESIS Edited by Kathryn Tonissen Carcinogenesis http://dx.doi.org/10.5772/2982 Edited by Kathryn Tonissen Contributors Francesca. www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Carcinogenesis, Edited by Kathryn Tonissen p. cm. ISBN 978-953-51-0945-7 Contents Preface. describe clinical penetrance. c By biochemical testing (pentagastrin-stimulated calcitonin levels) is 95–100% by age 70. Table 1. Highly penetrant cancer syndromes Carcinogenesis 6 syndromes