Accession Number : ADA302257

Title :   Role of ERBB-2 in Breast Cancer Progression.

Descriptive Note : Annual rept. 1 Sep 94-31 Aug 95,

Corporate Author : GEORGETOWN UNIV WASHINGTON DC

Personal Author(s) : Kern, Francis G.

PDF Url : ADA302257

Report Date : SEP 1995

Pagination or Media Count : 14

Abstract : Overexpression of growth factors and growth factor receptors is frequently associated with loss of estrogen receptor (ER) in human breast cancer, leading to the hypothesis that constitutive expression of these proteins might decrease dependence on estrogen. We have previously investigated the role of one putative growth factor receptor, c-erbE-2, in loss of hormone dependence by transfection of the c-erbB-2 cDNA into ER+ human breast cancer cells. We found that the size of the tumors formed correlated with the degree of tyrosine phosphorylation of the transfected protein. We hypothesized that an increase in tyrosine phosphor- ylation might increase the tumorigenicity of the cells. We therefore transfected ER+ MCF-7 cells with wild type and constitutively active mutant c-erbB-2 cDNAs. We found that we were able to stably overexpress the wild type protein only in the absence of estrogen, and that we were unable to stably overexpress the mutant protein under any growth conditions. Subsequent transfection of the mutant c-erbB-2 using a tetracycline-regulated gene expression system suggested that constitutive expression of this protein might induce apoptosis in breast cancer cells. These results suggest an important role for c-erbB-2 in regulation of the growth of breast cancer cells.

Descriptors :   *HORMONES, *MAMMARY GLANDS, *GROWTH(PHYSIOLOGY), *ESTROGENS, *BREAST CANCER, ENVIRONMENTS, HUMANS, PROTEINS, MUTATIONS, LOSSES, HYPOTHESES, CELLS(BIOLOGY), WILDLIFE, SENSE ORGANS, TYROSINE, PHOSPHORS, PHOSPHORYLATION.

Subject Categories : Anatomy and Physiology
      Biochemistry

Distribution Statement : APPROVED FOR PUBLIC RELEASE