Accession Number:

ADA341503

Title:

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

Descriptive Note:

Annual rept. 1 Oct 96-30 Sep 97.

Corporate Author:

COLUMBIA UNIV NEW YORK

Personal Author(s):

• Calame, Kathryn L.

Report Date:

1997-10-01

Pagination or Media Count:

30.0

Abstract:

Our studies on transcriptional regulation of the c-myc proto-oncogen are divided into two subprojects i studies on Blimp-1, a transcriptional repressor of c-myc and ii studies to determine the mechanism by which estrogen induces c-myc transcription in estrogen-dependent breast cancer cells. Blimp-1 was initially identified as a master-regulator of B-lymphocyte differentiation and was thought to be B-cell specific. We recently showed that Blimp-1 is a site specific repressor of c-myc ye transcription. Our studies reported here provide evidence that Blimp-1 plays a role in terminal differentiation of many cell lineages. We show that Blimp-1 mRNA is induced upon terminal differentiation of promyelocytic cells in culture and that Blimp-1 mRNA is present in many adult tissues. We have also demonstrated the ability of Blimp-1 to repress growth of MCF-7 breast cancer cells, which depend upon c-Myc activity for their transformed growth. In the second project, runon transcription has been used to show that estrogen induces transcription initiation but does not alter polymerase processivity on the c-myc gene in MCF-7 cells. We have identified four DNaseI hypersensitivity sites in the c-myc gene which are induced in response to estrogen. They are good candidates to be unusual estrogen response elements.

Descriptors:

• *ESTROGENS
• *BREAST CANCER
• TISSUES(BIOLOGY)
• HUMANS
• RESPONSE
• ADULTS
• HYPERSENSITIVITY

Subject Categories:

• Biochemistry
• Anatomy and Physiology

Distribution Statement:

APPROVED FOR PUBLIC RELEASE