Mechanisms for c-myc Induced Mouse Mammary Gland Carcinogenesis and for the Synergistic Role of TGF(alpha) in the Process
Annual summary rept. 1 Jul 2000-30 Jun 2001
GEORGETOWN UNIV WASHINGTON DC MEDICAL CENTER
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This project aims to elucidate the cell cycle basis on which c-myc oncogene induces mammary carcinogenesis and transforming growth factor alpha tgf-Alpha promotes the process. Conduction of this training project will help the P.I. to develop his career in breast cancer research. Data obtained so far have shown that c-myc transgenic mammary tumors may develop specific foci that are more aggressive than their adjacent tumor areas and thus represent a second stage of tumor progression. c-Myc may induce E2F1 and cyclin A2 to initiate the tumor development, whereas overexpression of cyclins D1 and E may occur as later events to promote tumor progression to a more aggressive phenotype. TGF-Alpha may enhance c-Myc-induced mammary carcinogenesis by inducing cyclin D1 and facilitating the loss of pRB expression, resulting in an earlier development of more aggressive tumors in tgf-Alphac-myc double transgeneic mice, compared to the c-myc tumors. These findings in the transgenic animals may have relevance to human breast cancer.
- Anatomy and Physiology
- Medicine and Medical Research