Regulation and Mechanism of Action of the c-Myc Proto- Oncogene in Human Breast Cancer

摘要

c-Myc is one of the proto-oncogenes which is known to play a role in breast cancer. c-Myc is elevated in both hormone-dependent and hormone- independent breast cancers and the causes of dysregulation appear to differ. In this work, we have focused on three different aspects of c-Myc regulation and mechanism of action. First, we have shown that one mechanism by which c-Myc acts is to associate with the transcription regulator YY1 and inhibit its ability to regulate transcription. Our data suggest that this mechanism is particularly important in situations in which c-Myc levels are elevated. Second, we have identified a new repressor of c-Myc transcription. There is strong evidence that this protein, Blimp-1, is important during terminal differentiation of B lymphocytes; however, we also present evidence suggesting that it may be involved in terminal differentiation of many other lineages. As a repressor of c-Myc transcription, Blimp-1 is a good candidate for a tumor suppressor. Finally, we have studied the mechanisms responsible for estrogen-dependent induction of c-Myc in hormone-dependent breast cancer cell lines. Our data show that estrogen increases both the initiation and processivity of c-myc transcription.