Accession Number : ADA328873

Title :   HER-2 as a Progression Factor and Therapeutic Target in Breast Cancer

Descriptive Note : Annual rept. 1 May 96-30 Apr 97

Corporate Author : GEORGETOWN UNIV WASHINGTON DC

Personal Author(s) : Czubayko, Frank

PDF Url : ADA328873

Report Date : JUN 1997

Pagination or Media Count : 25

Abstract : We studied the effect of down-regulation of HER-2 expression by ribozyme-targeting on in vitro and in vivo proliferation of cancer cells. We found that colony formation in soft agar was dependent on HER-2 expression in MCF-7 breast cancer cells and SK-OV-3 ovarian cancer cells. The exciting and surprising observation that colony formation of MCF-7 cells is dependent on HER-2 expression demonstrates that already low levels of endogenous HER-2 expression can have a significant impact on breast cancer growth. We studied the molecular mechanisms responsible for these effects and found that heregulin (ligand for HER-3 and HER-4) mediated stimulation of colony formation depends on HER-2 expression in MCF-7 cells and that EGF (ligand for HER-1)-mediated stimulation of colony formation in SK-OV-3 cells is dependent on HER-2. This indicates that HER-2 is the rate limiting receptor in most heterodimeric HER-receptor complexes. Finally, HER-2 activation is not necessary to stimulate mitogenesis but is required to prevent the cells from undergoing apoptosis. Our most striking result is the observation that depletion of HER-2 prevents estradiol mediated stimulation of colony formation in MCF-7 breast cancer cells. This demonstrates the direct cross-talk between the two pathways and furthermore, that activation of a growth factor pathway is required for estradiol mediated stimulation of proliferation.

Descriptors :   *HORMONES, *NEOPLASMS, *GROWTH(PHYSIOLOGY), *BREAST CANCER, PEPTIDES, PROTEINS, TARGETS, IN VITRO ANALYSIS, GENES, IN VIVO ANALYSIS, CELLS(BIOLOGY), RIBONUCLEIC ACIDS, AMINO ACIDS, TYROSINE, PHOSPHORUS TRANSFERASES, TRANSFECTION.

Subject Categories : Biochemistry
      Genetic Engineering and Molecular Biology
      Medicine and Medical Research

Distribution Statement : APPROVED FOR PUBLIC RELEASE