The Role of Heparin-Binding EGF-Like Growth Factor in Breast Cancer.
Abstract
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family which binds to and activates the EGF receptor. Its role in breast cancer, however, is unclear. We have studied the mechanism of induction of HB-EGF(by EGF(in the spontaneously immortalized mammary epithelial cell line MCF-10A and in MCF-10A cells that have been transformed with oncogenic Ha-ras. The levels of EGFR, erbB-2 and erbB-3 were very similar in the nontransformed and in the transformed MCF-10A cells. However, the levels of mitogen- activated protein kinase (MAPK) were elevated in the MCF-10A cells transformed with the Ha-ras oncogene. Neutralizing antibodies and inhibitors against the EGFR were able to inhibit the induction of HE-EUF mRNA levels in the nontransformed MCF-10A cells but not in the MCF- lOA cells transfected with oncogenic Ha-ras. However, an inhibitor of MAPK kinase (MEK) completely blocked the EOF induction of HB-EOF mRNA levels in the parental MCF-10A cells as well as in transformed MCF-10A cells, which suggests that EUF may be operating through other erbB receptors such as erbB-2/erbB-3 heterodimers and that MAPK is involved in the i,of induction in nontransformed and transformed human mammary
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1997
- Accession Number
- ADA341228
Entities
People
- David S. Salomon
Organizations
- National Institutes of Health