Regulation and Mechanism of Action of the C-MYC Proto-Oncogene in Human Breast Cancer.
Annual rept. 1 Oct 94-30 Sep 95,
COLUMBIA UNIV NEW YORK
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The biological relevance of the c-MycYY1 association has been established by demonstrating that the two proteins associate in vivo and showing that the amount of YY1 associated with c-Myc varies when c-Myc levels change. We have also shown that association with c-Myc does not inhibit the ability of YY1 to bind DNA, but appears to alter its ability to associate with basal transcription proteins TBP and TF-IIB. Steady-state c-myc RNA in MCF-7 cells was shown to increase approximately 1OX in response to estrogen. We expect that at least part this effect depends on transcription because we have identified two estrogen-dependent DNase I hypersensitive sites in the c-myc gene. One of these maps to a region containing NF-kB and CEBP sites. We are exploring how these proteins may mediate a response to estrogen. Finally, we have shown that PRDIBFIBlimp-1 is a repressor of c-myc transcription. We are exploring its mechanism of action and determining how overexpression of the gene may alter the growth phenotype of various breast tumor cell lines.
- Anatomy and Physiology
- Medicine and Medical Research