Molecular Basis of Breast Cancer : Prevention and Treatment

by Russo, Jose

• ISBN13: 9783540003915
• ISBN10: 3540003916
• Edition: 1st
• Format: Hardcover
• Copyright: 2003-12-01
• Publisher: SPRINGER

Summary

This richly illustrated atlas-like book provides a foundation for the biological and molecular understanding of how the mammary gland develops and how breast cancer originates. The main goal is to comprehensively review in ten chapters fundamental knowledge in breast cancer. New paradigms are described in which induction of differentiation in the mammary gland can promote prevention and cure of breast cancer. The book is extremely helpful both for clinicians treating patients and researchers looking for new avenues of development.

Table of Contents

Epidemiological Considerations in Breast Cancer
Introduction	1	(1)
Geographical Influences	1	(1)
Radiation as an Etiologic Agent	2	(1)
Electromagnetic Fields	2	(1)
Environmental Pollutants	3	(1)
Reproductive Factors	3	(1)
Environmental Exposures at a Young Age that Increase the Risk of Breast Cancer	4	(2)
Endocrinological Milieu	4	(1)
Smoking	4	(1)
Alcohol as a Neuroendocrine Disruptor	5	(1)
Effect of Light on Puberty and Breast Cancer Risk	5	(1)
Conclusions	6	(5)
References	6	(5)
The Breast as a Developing Organ
Introduction	11	(1)
Prenatal and Perinatal Development	12	(3)
Postnatal Development	15	(7)
Pregnancy	22	(4)
Postlactational Changes	26	(1)
The Menopausal Breast	26	(3)
Parenchyma-Stroma Relationship	29	(1)
Genetic Influences in Breast Development	30	(1)
Cell Proliferation and Hormone Receptors in Relation to Breast Structure	31	(1)
Extracellular Matrix Protein Expression in the Normal Breast	32	(4)
Angiogenic Index in the Lobular Structures	32	(2)
Elastin in the Lobular Structures	34	(1)
Tenascin in the Lobular Structures	35	(1)
Genomic Profile of Lobular Structures in Nulliparous and Parous Women's Breasts	36	(4)
Novel Differentiation-Associated Serpin is Upregulated During Lobular Development	40	(5)
Mammary-Derived Growth Inhibitor	45	(1)
Conclusions	45	(4)
References	46	(3)
Endocrine Control of Breast Development
Introduction	49	(2)
Steroid Receptors, Cell Proliferation, and Breast Differentiation	51	(6)
Relationship of Proliferating and ERα-Positive Cells in the Human Breast	53	(1)
Cell Proliferation, ERα, and PgR Content in the Rat Mammary Gland	53	(2)
Biological Significance	55	(2)
Human Chorionic Gonadotropin as a Differentiating Agent in the Human Breast and in the Rodent Mammary Gland	57	(4)
Evidence for a Receptor for Human Chorionic Gonadotropin in Human Breast Epithelial Cells	57	(3)
Human Chorionic Gonadotropin Receptor in the Rat Mammary Gland	60	(1)
Biological Significance of the LH/hCG Receptor	60	(1)
Effect of Human Chorionic Gonadotropin on Human Breast Epithelial Cells	61	(10)
Effect on Protein Synthesis and In Vitro Translational Products of mRNA	61	(3)
Effect of Human Chorionic Gonadotropin Treatment on Inhibin Synthesis	64	(4)
Effect of Hormones on the Proliferative Activity of Cultured Normal and Neoplastic Human Breast Epithelial Cells	68	(1)
Biological Significance of the hCG-Inhibin Pathway	69	(2)
Homeobox Genes' Expression and Their Modulation by Human Chorionic Gonadotropin in Human Breast Epithelial Cells	71	(7)
Class I Homeobox Gene Expression in Human Breast Epithelial Cell Lines	72	(1)
Human Chorionic Gonadotropin Modulates Expression of Homeobox Genes	73	(1)
Human Chorionic Gonadotropin and HOXA2 Inhibit AP-1	74	(4)
Human Chorionic Gonadotropin and Histone Acetylation	78	(2)
Conclusions	80	(9)
References	81	(8)
The Role of Estrogen in Breast Cancer
Introduction	89	(1)
Sources of Estrogens in Human Breast Tissue	90	(4)
Role of Estrogens in Human Breast Proliferation	94	(1)
Estrogens in Human Breast Carcinogenesis	95	(7)
Receptor-Mediated Pathway	96	(2)
Oxidative Metabolism of Estrogen	98	(2)
Estrogen as Mutagenic Agents	100	(1)
The Mechanism by Which Estrogens Induce Mutations	100	(1)
Additional Factors Contributing to the Carcinogenic Effect of Estrogen	100	(1)
Estrogens as Inducers of Aneuploidy	101	(1)
Biological Demonstration That Estrogens Are Carcinogenic in the Human Breast	102	(26)
The Proof of Principle	102	(1)
The In Vitro Model of Cell Transformation	102	(1)
Transformation Effect of Estrogen in MCF-10F Cells	102	(4)
Transformation Effect of the Estrogen Metabolites	106	(3)
Role of Antiestrogens in the Expression of the Transformation Phenotype	109	(2)
Detection of Estrogen Receptors in MCF 10F-Cells	111	(1)
Evidence for a Role of ERβ and Metabolic Activation of Estrogen in the Transformation of Human Breast Epithelial Cells	112	(1)
Genomic Changes Induced by Estrogen and Its Metabolites in Human Breast Epithelial Cells	113	(5)
Other Genomic Changes Induced by Estrogen and Its Metabolites in the Transformation of Human Breast Epithelial Cells	118	(6)
Chromosomal Alterations Induced by Estrogen and Its Metabolites	124	(4)
A Unified Concept in the Role of Estrogen in Breast Cancer	128	(9)
References	128	(9)
Pathogenesis of Breast Cancer
Introduction	137	(1)
The Site of Origin of Breast Cancer	137	(2)
Supporting Evidence for the Site of Origin of Breast Cancer	139	(11)
In Vitro Studies	139	(3)
Breast Architecture as a Determining Factor in the Susceptibility of the Human Breast to Cancer	142	(5)
Specific Considerations on the Relation Between Lobular Development and Familial Breast Cancer-Related Genes	147	(2)
Unifying Concepts	149	(1)
Molecular Changes in the Initiation and Progression of Breast Cancer	150	(17)
Differential Expression of Human Ferritin H Chain Gene and Breast Cancer	150	(3)
S100P Calcium-Binding Protein as a Marker of Cancer Initiation	153	(8)
Role of Intracellular Ca2+ During Cell Immortalization and Cell Transformation	161	(3)
The Role of Ca Intracellular and S100 Protein Expression in the Formation of Microcalcifications in Preneoplastic and Neoplastic Lesions of the Breast	164	(3)
Genetic Changes Associated with Initiation and Progression of Breast Cancer	167	(8)
Laser Capture Microdissection	168	(3)
Microsatellite Instability and Loss of Heterozygosity in Microdissected Lesions of the Breast	171	(1)
Example of Breast Cancer Genetic Heterogeneity Revealed by Laser Capture Microdissection Technique	172	(3)
Summary and Conclusions	175	(6)
References	176	(5)
Animal Models for Human Breast Cancer
Introduction	181	(1)
General Concepts	181	(1)
Chemically-Induced Mammary Tumorigenesis	182	(1)
Radiation-Induced Mammary Tumorigenesis	183	(2)
Genetic Background and Mammary Carcinogenesis	185	(1)
Pathogenesis of Rat Mammary Tumors	185	(6)
Mammary Gland Differentiation as a Modulator of Carcinogenic Response	191	(18)
Cell of Origin of Rat Mammary Carcinomas	195	(4)
Cell Kinetics and Mammary Carcinogenesis	199	(5)
Role of the Stroma in the Pathogenesis of Mammary Cancer	204	(5)
Pathological Classification of Rat Mammary Tumors	209	(9)
Epithelial Neoplasms	210	(1)
Intraductal Papilloma	210	(1)
Papillary Cystadenoma	210	(1)
Adenoma	210	(1)
Precancerous Lesions: Intraductal Proliferation	210	(2)
Carcinoma In Situ	212	(1)
Invasive Ductal Carcinomas	212	(4)
Stromal Neoplasms	216	(1)
Fibroma	216	(1)
Fibrosarcoma	216	(1)
Epithelial-Stromal Neoplasms	217	(1)
Fibroadenoma	217	(1)
Carcinosarcoma	218	(1)
Nonneoplastic Lesions	218	(1)
Differential Diagnosis of Mammary Tumors	218	(2)
Macroscopic Criteria	220	(1)
Histopathological Criteria	220	(1)
Biological Criteria	220	(1)
Biological Importance of the Chemical Carcinogen-Induced Rat Mammary Tumor Model	220	(1)
Genetically Engineered Mice Model	221	(6)
Anatomy of the Mouse Mammary Gland	221	(3)
Classification of Genetically Engineered Mouse Mammary Lesions	224	(1)
Comparative Pathology of the Model Systems	224	(1)
References	225	(2)
In Vitro Models for Human Breast Cancer
Introduction	227	(1)
Growth Properties of Normal Human Breast Epithelial Cells In Vitro	227	(3)
The MCF-7 Cell as a Model of Human Breast Cancer In Vitro	230	(11)
Morphological and Growth Characteristics of MCF-7 Cells	230	(3)
Growth of MCF-7 Cells in Tridimensional Matrix	233	(4)
Growth of MCF-7 Cells in Athymic Mice	237	(4)
Growth Properties of Immortal Human Breast Epithelial Cells In Vitro	241	(9)
Telomerase Activation	243	(1)
Abrogation of Cell Cycle Control	243	(4)
Genes Preferentially Expressed During Cell Immortalization	247	(3)
Transformation of Primary Cultures of Human Breast Epithelial Cells with Chemical Carcinogens	250	(2)
In Vitro System of Cell Transformation	252	(29)
Transformation of Human Breast Epithelial Cells with c-Ha-ras Oncogene	252	(9)
Transformation of Human Breast Epithelial Cells with Chemical Carcinogens	261	(8)
Ha-ras Enhances the Transformation of Human Breast Epithelial Cells with Chemical Carcinogens	269	(4)
References	273	(8)
Genomic Basis of Breast Cancer
Introduction	281	(1)
Genomic Changes Observed in Breast Cancer	281	(3)
Microsatellite Instability as an Early Genomic Event in Breast Cancer Initiation	284	(4)
Other Genomic Changes Associated with Immortalization, Transformation, and Tumorigenesis	288	(4)
Tumor Suppressor Gene p53	288	(1)
Oncogenes	289	(1)
c-Ha-ras	289	(1)
c-neu, int-2, and c-myc Oncogenes	289	(1)
mdm2 Gene	290	(1)
Loss of Heterozygosity and Fluorescence In Situ Hybridization Analysis of Chromosome 17p	291	(1)
Search for Specific Functional Relevance of the Genomic Changes	292	(15)
Reversion of the Immortalization Phenotype	292	(10)
Reversion of the Transformation but Not Immortalization Phenotype	302	(5)
The Role of Mismatch Repair in the Initial Event of Carcinogenesis	307	(3)
Unifying Concepts	310	(7)
References	311	(6)
Preventive Strategies in Breast Cancer
Introduction	317	(3)
Physicoprevention with Prophylactic Mastectomy	320	(1)
Bioprevention of Hereditary Breast Cancer	320	(1)
Chemoprevention Against Acquired Somatic Mutations	321	(14)
Limiting Accumulation of Chemical Carcinogens	323	(1)
Enhancing Excretion of Xenobiotics	324	(1)
Organosulfur Compounds	324	(2)
Indole-3-Carbinol	326	(1)
Phytoalexin	327	(1)
Triterpenoids	328	(1)
Eliminating Oxidative Stress	328	(1)
Carotenoids	328	(2)
Vitamin E and Selenium	330	(2)
Tea and Polyphenolic Antioxidants	332	(1)
Flavonoids	333	(2)
Chemoprevention Against Epigenetic Alterations	335	(6)
Restricting Fat/Caloric Consumption	335	(1)
Maintaining Proper Endocrine Milieu	336	(1)
Steroids	336	(2)
Aromatase Inhibitors	338	(1)
Estrone Sulfatase Inhibitors	339	(1)
Dehydroepi and roster one	340	(1)
Genistein	340	(1)
Melatonin	341	(2)
Eicosanoids	343	(2)
Estrogen Antagonists	345	(2)
Antiestrogens	345	(1)
Aryl Hydrocarbon Receptor Agonists	346	(1)
Interrupting Carcinogenic Signal Transduction	347	(5)
Inhibitors of Receptor Tyrosine Kinases	347	(3)
Inhibitors of p21ras Farnesylation	350	(1)
Inhibitors of HMG-CoA Reductase	351	(1)
Monoterpenes	351	(1)
Eicosapentaenoic Acid	352	(1)
Inducing Breast Cell Differentiation	352	(2)
Retinoids	352	(2)
Pregnancy and Human Chorionic Gonadotropin	354	(1)
N-Chemoprevention Against Growth of Neoplasms: Suppressing the Growth of Neoplastic Cells	354	(4)
Vitamin D and Calcium	354	(2)
Ornithine Decarboxylase Inhibitors	356	(2)
O-Inhibiting Neovascularization or Angiogenesis	358	(1)
Socioprevention of Breast Cancer	358	(1)
Summary and Future Perspectives	359	(20)
References	360	(19)
The New Paradigm in Breast Cancer Prevention Rationale for a New Paradigm	379	(60)
The New Paradigm	379	(1)
Epidemiological and Clinical Basis for the New Paradigm	380	(1)
Data from Experimental Animal Studies	381	(11)
Pregnancy	381	(1)
Placental Hormones	382	(3)
Estrogenic and Progestagenic Agents	385	(2)
Role of Pregnancy and Chorionic Gonadotropin in Mammary Gland Differentiation and Cancer Initiation	387	(5)
Role of Human Chorionic Gonadotropin in Breast Cancer Progression	392	(7)
Mammary Gland Development Under Influence of Human Chorionic Gonadotropin	393	(3)
Hormonal Profile Induced by Human Chorionic Gonadotropin	396	(1)
Effect of Human Chorionic Gonadotropin on Terminal End Buds, Intraductal Proliferations, and Ductal Carcinomas In Situ	397	(1)
Effect of Human Chorionic Gonadotropin Treatment on DMBA-Induced Tumor Progression	398	(1)
Effect of Human Chorionic Gonadotropin on Inhibin Expression and Its Relation with the Activation of Early Response Genes	399	(5)
Effect of Human Chorionic Gonadotropin on Programmed Cell Death Gene Expression	404	(7)
Effect of Human Chorionic Gonadotropin in the Mammary Gland of Animals Treated with DMBA	404	(4)
Effect of Human Chorionic Gonadotropin Treatment on the Expression of Apoptotic Genes in DMBA-Induced Mammary Carcinomas	408	(1)
Effect of Human Chorionic Gonadotropin Treatment on the Expression of Apoptotic Genes in the Ovary	408	(2)
Effect of Human Chorionic Gonadotropin Treatment on Apoptosis	410	(1)
Evidence of a Direct Effect of Human Chorionic Gonadotropin in Mammary Epithelial Cells	411	(6)
Human Chorionic Gonadotropin Has an Inhibitory Effect on DMBA Mammary Carcinogenesis in Ovariectomized Animals	411	(1)
Effect of Human Chorionic Gonadotropin in Human Breast Epithelial Cells In Vitro	412	(5)
Tumoristatic Effect of Human Chorionic Gonadotropin on Malignant Human Breast Epithelial Cells Transplanted in Heterologous Host	417	(1)
Effect of Recombinant Human Choronic Gonadotropin on Primary Breast Cancer	417	(2)
Isolation and Characterization of New Genes Induced by Human Chorionic Gonadotropin	419	(11)
Genes Induced by Human Chorionic Gonadotropin in Human Breast Epithelial Cells In Vitro	419	(4)
Genes Induced by Human Chorionic Gonadotropin in the Rat Mammary Gland	423	(3)
Morphological Phenotypes Induced by Urinary and Recombinant Human Chorionic Gonadotropin	426	(1)
Differential Display and Northern Blot Analysis	426	(4)
Genomic Signature Induced by Human Chorionic Gonadotropin and Pregnancy	430	(2)
Unifying Concepts	432	(7)
References	433	(6)
Subject Index	439