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Genetic mechanisms that promote breast preneoplasia and cancer development
1993- Conversion of a normal mammary epithelial cell to a cancer cell is caused by modifications of the cellular machinery that regulate normal cell growth and differentiation. Genetic factors influence susceptibility to this conversion and estrogen pathways are critically involved in the initiation of many types of breast cancer. Most recently the Furth Lab found that Cyclin D1 is required for ERalpha-disease initiation, p53 deficiency influences the probability of pregnancy-associated cancer protection in ERalpha-initiated disease, and that Stat5a deficiency impacts susceptibility to carcinogen-induced breast disease. On-going studies are examining the altered epithelial-stromal cross-talk induced by over-expression of the SRC3/AIB1 splice variant AIB1delta3, the differences in downstream signaling between ERalpha, aromatase over-expression in mammary epithelial cells, impact on Brca1 loss on mammary differentiation and cell fate and impact of aberrations in the cyclin-CDK-RB on progression of preneoplasia. |
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