Transgenic mouse models of human breast cancer

The pathogenesis of human breast cancer is thought to involve multiple genetic events, the majority of which fall into two categories, gain of function mutations in proto-oncogenes such as c-myc, cyclin D1, ErbB-2 and various growth factors which are involved in supporting cell growth, division and survival, and loss of function mutations in so called ‘tumor suppressor’ genes, such as p53, which are involved in preventing unrestrained cellular growth. A number of mouse systems exist to address the significance of these mutations in the pathogenesis of breast cancer including transgenic mice expressing high levels of a specific gene in target tissues and knockout mice in which specific genes have been ablated via homologous recombination. More recently, the combination of these techniques to create bigenics as well as the use of ‘knockin’ and conditional tissue specific gene targeting strategies have allowed the models more reflective of the human disease to be devised. Studies with these models have not only implicated particular genetic events in the progression of the disease but have emphasized the complex, multi-step nature of breast cancer progression. These models also provide the opportunity to study various aspects of the pathogenesis of this disease, from hormonal effects to responses to chemotherapeutic drugs. It is hoped that through the combined use of these models, and the further development of more relevant models, that a deeper understanding of this disease and the generation of new therapeutic agents will result.

[1]  J. Foekens,et al.  Prognostic factors in human primary breast cancer: Comparison of c-myc and HER2/neu amplification , 1992, The Journal of Steroid Biochemistry and Molecular Biology.

[2]  W D Dupont,et al.  Risk factors for breast cancer in women with proliferative breast disease. , 1985, The New England journal of medicine.

[3]  B. Li,et al.  neu/ERBB2 cooperates with p53-172H during mammary tumorigenesis in transgenic mice , 1997, Molecular and cellular biology.

[4]  Kristen L Murphy,et al.  Cooperative interaction between mutant p53 and des(1-3)IGF-I accelerates mammary tumorigenesis , 2000, Oncogene.

[5]  Richard J. Lee,et al.  pp60(v-src) induction of cyclin D1 requires collaborative interactions between the extracellular signal-regulated kinase, p38, and Jun kinase pathways. A role for cAMP response element-binding protein and activating transcription factor-2 in pp60(v-src) signaling in breast cancer cells. , 1999, The Journal of biological chemistry.

[6]  B. Hogan,et al.  Distinctive patterns of hyperplasia in transgenic mice with mouse mammary tumor virus transforming growth factor-alpha. Characterization of mammary gland and skin proliferations. , 1992, The American journal of pathology.

[7]  P. Leder,et al.  The int‐2 gene product acts as an epithelial growth factor in transgenic mice. , 1990, The EMBO journal.

[8]  B. Elliott,et al.  Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma. , 1996, The American journal of pathology.

[9]  C. Liu,et al.  Inactivation of the mouse Brca1 gene leads to failure in the morphogenesis of the egg cylinder in early postimplantation development. , 1996, Genes & development.

[10]  G. Peters,et al.  The mouse homolog of the hst/k-FGF gene is adjacent to int-2 and is activated by proviral insertion in some virally induced mammary tumors. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[11]  P. Leder,et al.  Coexpression of MMTV/v-Ha-ras and MMTV/c-myc genes in transgenic mice: Synergistic action of oncogenes in vivo , 1987, Cell.

[12]  O. Brison,et al.  Gene amplification and tumor progression. , 1993, Biochimica et biophysica acta.

[13]  R. Cardiff,et al.  Transgenic expression of tpr-met oncogene leads to development of mammary hyperplasia and tumors. , 1996, The Journal of clinical investigation.

[14]  J. Paterson BRCA1: a review of structure and putative functions. , 1998, Disease markers.

[15]  B. O’Malley,et al.  Progesterone, in addition to estrogen, induces cyclin D1 expression in the murine mammary epithelial cell, in vivo. , 1997, Endocrinology.

[16]  W. Birchmeier,et al.  Reconstitution of Mammary Gland Development In Vitro: Requirement of c-met and c-erbB2 Signaling for Branching and Alveolar Morphogenesis , 1998, The Journal of cell biology.

[17]  Monilola A. Olayioye,et al.  The ErbB signaling network: receptor heterodimerization in development and cancer , 2000, The EMBO journal.

[18]  W. McGuire,et al.  Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. , 1987, Science.

[19]  R. Weinberg,et al.  The neu oncogene: an erb-B-related gene encoding a 185,000-Mr tumour antigen , 1984, Nature.

[20]  I. Bièche,et al.  Genetic alterations in breast cancer , 1995, Genes, chromosomes & cancer.

[21]  R. Palmiter,et al.  Overexpression of TGFα in transgenic mice: Induction of epithelial hyperplasia, pancreatic metaplasia, and carcinoma of the breast , 1990, Cell.

[22]  Walter Gilbert,et al.  Ligands for ErbB-family receptors encoded by a neuregulin-like gene , 1997, Nature.

[23]  M. Rudnicki,et al.  Amplification of the neu/erbB-2 oncogene in a mouse model of mammary tumorigenesis. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[24]  P. Leder,et al.  Single-step induction of mammary adenocarcinoma in transgenic mice bearing the activated c-neu oncogene , 1988, Cell.

[25]  L. Donehower,et al.  Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours , 1992, Nature.

[26]  Emma Lees,et al.  Mammary hyperplasia and carcinoma in MMTV-cyclin D1 transgenic mice , 1994, Nature.

[27]  C. MacArthur,et al.  MMTV-Fgf8 transgenic mice develop mammary and salivary gland neoplasia and ovarian stromal hyperplasia , 1998, Oncogene.

[28]  R. Cardiff,et al.  Transgenic mouse models of mammary tumorigenesis. , 1993, Cancer surveys.

[29]  S. Bull,et al.  neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[30]  W. McGuire,et al.  Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer. , 1992, Human pathology.

[31]  W. Birchmeier,et al.  Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland , 1995, The Journal of cell biology.

[32]  B. Groner,et al.  Targeted c‐myc gene expression in mammary glands of transgenic mice induces mammary tumours with constitutive milk protein gene transcription. , 1988, The EMBO journal.

[33]  G. Merlo,et al.  Somatic mutations and human breast cancer. A Status Report , 1992, Cancer.

[34]  W. Muller,et al.  Mutations affecting conserved cysteine residues within the extracellular domain of Neu promote receptor dimerization and activation. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[35]  M. Hung,et al.  A novel splice variant of HER2 with increased transformation activity , 1998, Molecular carcinogenesis.

[36]  Thomas Ried,et al.  Conditional mutation of Brca1 in mammary epithelial cells results in blunted ductal morphogenesis and tumour formation , 1999, Nature Genetics.

[37]  R. Lidereau,et al.  Genetic variability of proto-oncogenes for breast cancer risk and prognosis. , 1988, Biochimie.

[38]  M. Fiscella,et al.  The mutationally activated Met receptor mediates motility and metastasis. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[39]  Y. Yarden,et al.  Cyclin D1 Is Required for Transformation by Activated Neu and Is Induced through an E2F-Dependent Signaling Pathway , 2000, Molecular and Cellular Biology.

[40]  P. Leder,et al.  Spontaneous mammary adenocarcinomas in transgenic mice that carry and express MTV/myc fusion genes , 1984, Cell.

[41]  G. G. Stokes "J." , 1890, The New Yale Book of Quotations.

[42]  R. Laucirica,et al.  Loss of anti-mitotic effects of Bcl-2 with retention of anti-apoptotic activity during tumor progression in a mouse model , 1999, Oncogene.

[43]  P. Jolicoeur,et al.  Stochastic appearance of mammary tumors in transgenic mice carrying the MMTV/c-neu oncogene , 1989, Cell.

[44]  C. MacArthur,et al.  Fgf-8, activated by proviral insertion, cooperates with the Wnt-1 transgene in murine mammary tumorigenesis , 1995, Journal of virology.

[45]  H. Wennbo,et al.  The role of prolactin and growth hormone in breast cancer , 2000, Oncogene.

[46]  P. Ravdin,et al.  The c-erbB-2 proto-oncogene as a prognostic and predictive marker in breast cancer: a paradigm for the development of other macromolecular markers--a review. , 1995, Gene.

[47]  R. Weinberg,et al.  p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity , 1986, Molecular and cellular biology.

[48]  G. Peters,et al.  Tumorigenesis by mouse mammary tumor virus: Proviral activation of a cellular gene in the common integration region int-2 , 1984, Cell.

[49]  P. Ravdin,et al.  Prognostic factors in early breast carcinoma , 1994, Cancer.

[50]  R. Palmiter,et al.  Inhibition of mammary gland involution is associated with transforming growth factor alpha but not c-myc-induced tumorigenesis in transgenic mice. , 1995, Cancer research.

[51]  B. Groner,et al.  An activated allele of the c-erbB-2 oncogene impairs kidney and lung function and causes early death of transgenic mice , 1993, The Journal of cell biology.

[52]  W Godolphin,et al.  Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. , 1989, Science.

[53]  W. Muller,et al.  Signal transduction in mammary tumorigenesis: a transgenic perspective , 2000, Oncogene.

[54]  S. Ritland,et al.  Loss of heterozygosity analysis in primary mammary tumors and lung metastases of MMTV-MTAg and MMTV-neu transgenic mice. , 1997, Cancer research.

[55]  Cori Bargmann,et al.  The neu oncogene encodes an epidermal growth factor receptor-related protein , 1986, Nature.

[56]  Cori Bargmann,et al.  Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185 , 1986, Cell.

[57]  N. Hynes,et al.  The biology of erbB-2/neu/HER-2 and its role in cancer. , 1994, Biochimica et biophysica acta.

[58]  S. Hilsenbeck,et al.  Increased tumor proliferation and genomic instability without decreased apoptosis in MMTV-ras mice deficient in p53 , 1997, Molecular and cellular biology.

[59]  G. Shackleford,et al.  Preferential activation of Fgf8 by proviral insertion in mammary tumors of Wnt1 transgenic mice , 1997, Oncogene.

[60]  B. Sauer Inducible gene targeting in mice using the Cre/lox system. , 1998, Methods.

[61]  P. Edwards,et al.  Impaired mammary gland development in Cyl-1(-/-) mice during pregnancy and lactation is epithelial cell autonomous. , 1999, Developmental biology.

[62]  P. Leder,et al.  Consequences of widespread deregulation of the c-myc gene in transgenic mice: Multiple neoplasms and normal development , 1986, Cell.

[63]  S. Dedhar,et al.  Overexpression of the Integrin-linked Kinase Promotes Anchorage-independent Cell Cycle Progression* , 1997, The Journal of Biological Chemistry.

[64]  R. Weinberg,et al.  Prolactin controls mammary gland development via direct and indirect mechanisms. , 1999, Developmental biology.

[65]  F. Kittrell,et al.  A transgenic mouse model for mammary carcinogenesis , 1998, Oncogene.

[66]  L. Amundadottir,et al.  Synergistic interaction of transforming growth factor alpha and c-myc in mouse mammary and salivary gland tumorigenesis. , 1995, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[67]  V. Godfrey,et al.  Mammary tumor formation in p53- and BRCA1-deficient mice. , 1999, Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research.

[68]  E. Lander,et al.  Mouse mammary tumor virus/v-Ha-ras transgene-induced mammary tumors exhibit strain-specific allelic loss on mouse chromosome 4. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[69]  E. Schröck,et al.  A recurring pattern of chromosomal aberrations in mammary gland tumors of MMTV‐cmyc transgenic mice , 1999, Genes, chromosomes & cancer.

[70]  L. Hennighausen,et al.  Transforming growth factor alpha and mouse models of human breast cancer , 2000, Oncogene.

[71]  R. Lidereau,et al.  Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[72]  F. Kittrell,et al.  Murine mammary gland carcinogenesis is critically dependent on progesterone receptor function. , 1999, Cancer research.

[73]  R. Cardiff,et al.  Activated neu Induces Rapid Tumor Progression (*) , 1996, The Journal of Biological Chemistry.

[74]  B. Hogan,et al.  Development of mammary hyperplasia and neoplasia in MMTV-TGFα transgenic mice , 1990, Cell.

[75]  R. Cardiff,et al.  Synergistic interaction of the Neu proto-oncogene product and transforming growth factor alpha in the mammary epithelium of transgenic mice , 1996, Molecular and cellular biology.

[76]  R. Cardiff,et al.  Elevated expression of activated forms of Neu/ErbB‐2 and ErbB‐3 are involved in the induction of mammary tumors in transgenic mice: implications for human breast cancer , 1999, The EMBO journal.

[77]  R. Peterson A nursing intervention for early detection of spinal cord compressions in patients with cancer , 1993, Cancer nursing.

[78]  D. Pinkel,et al.  Deficiency of p53 accelerates mammary tumorigenesis in Wnt-1 transgenic mice and promotes chromosomal instability. , 1995, Genes & development.

[79]  D. Salomon,et al.  Detection of amphiregulin and Cripto‐1 in mammary tumors from transgenic mice , 1996, Molecular carcinogenesis.

[80]  R. Cardiff,et al.  Expression of the neu protooncogene in the mammary epithelium of transgenic mice induces metastatic disease. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[81]  W. Muller,et al.  Novel activating mutations in the neu proto-oncogene involved in induction of mammary tumors. , 1994, Molecular and cellular biology.

[82]  G. Peters,et al.  Tumorigenesis by mouse mammary tumor virus: Evidence for a common region for provirus integration in mammary tumors , 1983, Cell.