The Role of Heparin-Binding EGF-Like Growth Factor in Breast Cancer.
Annual rept. 30 Sep 96-29 Sep 97,
NATIONAL INSTITUTES OF HEALTH BETHESDA MD
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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-EGFby EGFin 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-2erbB-3 heterodimers and that MAPK is involved in the i,of induction in nontransformed and transformed human mammary
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