TARGETING NEW PATHWAYS AND CELL DEATH IN BREAST CANCER Edited by Rebecca L. Aft Targeting New Pathways and Cell Death in Breast Cancer Edited by Rebecca L. Aft Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 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. 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Publishing Process Manager Silvia Vlase Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published February, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechweb.org Targeting New Pathways and Cell Death in Breast Cancer, Edited by Rebecca L. Aft p. cm. ISBN 978-953-51-0145-1 Contents Preface IX Part 1 Breast Cancer Cell Death 1 Chapter 1 Estrogen-Induced Apoptosis in Breast Cancer Cells: Translation to Clinical Relevance 3 Philipp Y. Maximov and V. Craig Jordan Chapter 2 Targeted Apoptosis in Breast Cancer Immunotherapy 23 Lin-Tao Jia and An-Gang Yang Chapter 3 Induction of Apoptosis in Human Cancer Cells by Human Eb- or Rainbow Trout Ea4-Peptide of Pro-Insulin-Like Growth Factor-I (Pro-IGF-I) 45 Maria J. Chen, Chun-Mean Lin and Thomas T. Chen Chapter 4 Induction of Autophagic Cell Death by Targeting Bcl-2 as a Novel Therapeutic Strategy in Breast Cancer 57 Bulent Ozpolat, Neslihan Alpay and Gabriel Lopez-Berestein Part 2 New Anti-Cancer Targets 69 Chapter 5 The ATF/CREB Family of Transcription Factors in Breast Cancer 71 Jeremy K. Haakenson, Mark Kester and David X. Liu Chapter 6 Newly-Recognized Small Molecule Receptors on Human Breast Cancer Cell Integrin αvβ3 that Affect Tumor Cell Behavior 85 Hung-Yun Lin, Faith B. Davis, Mary K. Luidens, Aleck Hercbergs, Shaker A. Mousa, Dhruba J. Bharali and Paul J. Davis Chapter 7 DNA Damage Response and Breast Cancer: An Overview 97 Leila J. Green and Shiaw-Yih Lin VI Contents Chapter 8 Cell Cycle Regulatory Proteins in Breast Cancer: Molecular Determinants of Drug Resistance and Targets for Anticancer Therapies 113 Aamir Ahmad, Zhiwei Wang, Raza Ali, Bassam Bitar, Farah T. Logna, Main Y. Maitah, Bin Bao, Shadan Ali, Dejuan Kong, Yiwei Li and Fazlul H. Sarkar Chapter 9 Multidrug Resistence and Breast Cancer 131 Gengyin Zhou and Xiaofang Zhang Chapter 10 Multiple Molecular Targets of Antrodia camphorata: A Suitable Candidate for Breast Cancer Chemoprevention 157 Hsin-Ling Yang, K.J. Senthil Kumar and You-Cheng Hseu Preface In this book we present manuscripts focusing on mechanisms of breast cancer cell death and new targets for therapeutic intervention by an accomplished group of international investigators. We have divided the book into 2 sections based on these topics. In the first section cell death by autophagy, estrogen induced apoptosis and by immunotherapy will be discussed. In the second section, there is an overview of the DNA damage response and discussion of new targets for intervention. Each of the experts contributing to this book discusses their topic thoughtfully and provides new insight into the topic leading to a new appreciation for these areas of investigation. Dr. Rebecca L. Aft Washington University School of Medicine Department of Surgery Saint Louis, Missouri USA [...]... goats and sheep Biochem J 72: 673-682 18 Targeting New Pathways and Cell Death in Breast Cancer Goss, P E., J N Ingle, et al (2005) Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17 J Natl Cancer Inst 97(17): 1262-1271 Gottardis, M M and V C Jordan (1987) Antitumor actions of keoxifene and tamoxifen in. .. Targeting New Pathways and Cell Death in Breast Cancer and results from intracellular signaling thereafter, which ultimately leads to the degradation of functional proteins, destroy of cytoskeletons and fragmentation of DNA (Hengartner, 2000; He et al, 2009) The major initiators, mediators and executioners involved in apoptotic signaling have been unraveled, which contribute to a better understanding... blocked estradiol-induced growth of ER-positive breast cancer cells in athymic mice 6 Targeting New Pathways and Cell Death in Breast Cancer (antiestrogenic action), but induced rapid growth of ER-positive endometrial carcinomas (estrogenic action) (Gottardis et al 1988); 4) raloxifene was less effective in promoting endometrial cancer growth than tamoxifen (less estrogenic action in uterine tissue) (Gottardis... tamoxifen metabolites 4-OHT and endoxifen Results show that our 12 Targeting New Pathways and Cell Death in Breast Cancer MCF-7:WS8 human breast cancer cells were exquisitely sensitive to E2 which produced a concentration-dependent increase in growth, and all of the TPE’s were potent agonists with the ability to stimulate MCF-7:WS8 breast cancer cell growth, however, their agonist potency was less compared... responsiveness of metastatic breast cancer following exhaustive antihormonal treatment 16 Targeting New Pathways and Cell Death in Breast Cancer with tamoxifen, aromatase inhibitors and etc 4 out of 32 patients had complete responses (Lonning et al 2001) and 1 patient after 5 year treatment with DES had no recurrence for a following 6 years (Lonning 2009) The question at that moment remains whether estrogen... with increased resistance to chemotherapy-induced apoptosis (Voehringer 1999) GSH is a water-soluble tripeptide composed of glutamine, cysteine, and glycine It is the most abundant intracellular small molecule thiol present in mammalian cells and it serves as a potent intracellular antioxidant protecting cells from toxins such as free radicals (Schroder et al 1996; Anderson et al 1999) Changes in GSH... tamoxifen-resistant breast cancer cells Int J Oncol 27(5): 1459-1466 Pink, J J., M M Bilimoria, et al (1996) Irreversible loss of the oestrogen receptor in T47D breast cancer cells following prolonged oestrogen deprivation Br J Cancer 74(8): 1227-1236 Pink, J J and V C Jordan (1996) Models of estrogen receptor regulation by estrogens and antiestrogens in breast cancer cell lines Cancer Res 56(10): 2321-2330... Targeting New Pathways and Cell Death in Breast Cancer was affiliated with significant systemic side effects, such as nausea, areola pigmentation, uterine bleeding, and edema of the lower extremities At approximately same time Walpole was investigating the role of diethylstilbestrol and dienestrol in breast cancer (Walpole 1948) He confirmed the results obtained by Haddow that estrogens are effective in. .. FasL binds and induces the trimerization of Fas, which in turn recruits the adaptor molecule Fas-associated death domain (FADD) via interaction between their death domains (DD) FADD also contains a death effector domain (DED), which aggregates and activates another DED-containing protein, FADD-like interleukin-1βconverting enzyme (FLICE)/caspase-8 This is followed by a cascade of caspase activation and. .. underlying physiological and pathological apoptosis, studies have been addressed in the development of pro-apoptotic strategies targeting the cancer cells, which has provided novel approaches to the successful immutherapy of breast cancers (Schlotter et al, 2008) 2 Unbalanced proliferation and apoptosis in breast cancers Cells undergo consistent proliferation and apoptosis during ontogenesis and in maintenance . TARGETING NEW PATHWAYS AND CELL DEATH IN BREAST CANCER Edited by Rebecca L. Aft Targeting New Pathways and Cell Death in Breast Cancer Edited by Rebecca. blocked estradiol-induced growth of ER-positive breast cancer cells in athymic mice Targeting New Pathways and Cell Death in Breast Cancer 6 (antiestrogenic action), but induced rapid growth. treat breast and prostate cancers Targeting New Pathways and Cell Death in Breast Cancer 4 was affiliated with significant systemic side effects, such as nausea, areola pigmentation, uterine