Accession Number : ADA332975

Title :   Her-2/Neu and Breast Cancer.

Descriptive Note : Annual rept. 8 Jul 96-7 Jul 97,

Corporate Author : OREGON HEALTH SCIENCES UNIV PORTLAND

Personal Author(s) : Doherty, Joni ; Clinton, Gail

PDF Url : ADA332975

Report Date : AUG 1997

Pagination or Media Count : 24

Abstract : Overexpression of the HER-2/neu proto-oncogene as a 185 kDa transmembrane tyrosine kinase occurs in approximately 30% of human breast and ovarian cancers and is associated, in a dose-dependent manner, with poor prognosis for survival of the patient. Although HER-2 gene amplification is a common mechanism for overexpression, many human tumors and cell lines display HER-2 mRNA and protein overexpression in excess of the level accountable by gene copy number, or in absence of gene amplification. Thus, mechanisms of transcriptional and post-transcriptional upregulation occur with respect to HER-2. Such mechanisms require further investigation with respect to human tumors and cell lines. Notably, the highest HER-2 protein-overexpressing cell line, 5k- OV-3, exhibits one of more of these mechanisms in addition to gene amplification. Furthermore, in addition to overexpression of the normal-sized 4.5 kb HER-2 mRNA transcript, SK-OV-3 also expresses an abundant alternative HER-2/neu transcript of 8 kb--the focus of my current research. Preliminary data demonstrates that this aberrant 8 kb transcript displays increased mRNA stability, and may have an altered 3'UTR sequence. The present work focuses on characterizing this transcript in terms of (1) structure/sequence, (2) origin, (3) mechanism(s) for accumulation in the cell, and (4) function.

Descriptors :   *CANCER, *OVARIES, *BREAST CANCER, HUMANS, NEOPLASMS, SURVIVAL(GENERAL), CHROMOSOMES, SEQUENCES, DISPLAY SYSTEMS, IMAGE INTENSIFICATION, PATIENTS, RECORDS, IMPACT PREDICTION, CELLS(BIOLOGY).

Subject Categories : Anatomy and Physiology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE