Mechanisms for c-myc Induced Mouse Mammary Gland Carcinogenesis and for the Synergistic Role of TGF(alpha) in the Process

摘要

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-Alpha/c-myc double transgeneic mice, compared to the c-myc tumors. These findings in the transgenic animals may have relevance to human breast cancer.