Accession Number : ADA303179

Title :   Identification of Mammary Specific Transcription Factors.

Descriptive Note : Annual rept. 30 Sep 94-29 Sep 95,

Corporate Author : NATIONAL CANCER INST BETHESDA MD

Personal Author(s) : Michelotti, Julia M.

PDF Url : ADA303179

Report Date : OCT 1995

Pagination or Media Count : 42

Abstract : The MMTV retrovirus causes mammary adenocarcinomas in mice by proviral insertion near members of the wnt family of proto-oncogenes, leading to their deregulation and cellular transformation. The 5' end of the MMTV LTR has been implicated in tissue-specific activation of these genes. In this study, we characterize an enhancer element (Ban2; -1075 to -978) at the 5' end of the MMTV LTR. We show that this enhancer is 5-fold more active in a murine mammary carcinoma cell line (34l) than in a fibroblast cell line (NIH3T3), and is inactive in the liver carcinoma cell line HepG2. Mutagenesis of the enhancer reveals four cis-acting elements that are required for maximal activity. DNA-binding proteins that interact with each of the four elements have been identified. One of these factors, designated mp5, is either identical to, or closely related to, the transcription factor AP-2. The mp5/AP-2 DNA-binding activity co-migrates with recombinant AP-2 and is supershifted by anti-AP-2 antibodies. We also show that the lack of enhancer activity in HepG2 cells results from the absence of AP-2 protein in these cells. Co-transfection of an AP-2 expression vector restores the activity of this enhancer in HepG2 cells.

Descriptors :   *TISSUES(BIOLOGY), *FIBROBLASTS, *CARCINOGENS, *MAMMARY GLANDS, *BREAST CANCER, CELLS, DEOXYRIBONUCLEIC ACIDS, MUTATIONS, GENES, MICE, TRANSFORMATIONS, GROWTH(PHYSIOLOGY), ONCOGENIC VIRUSES.

Subject Categories : Medicine and Medical Research
      Anatomy and Physiology

Distribution Statement : APPROVED FOR PUBLIC RELEASE