Abstract:
:Heparin-binding epidermal growth factor-like growth factor (HB-EGF) mRNA and protein expression is induced by EGF in MCF-10A nontransformed and Ha-ras transfected human mammary epithelial cells. The anti-EGF receptor (EGFR) blocking monoclonal antibody (MAb) 225 and the EGFR tyrosine kinase inhibitor PD153035 were able to inhibit the induction of HB-EGF mRNA levels in MCF-10A cells. However, the Ha-ras transformed MCF-10A cells were more refractory to inhibition by these agents and only a combination of the 225 MAb and PD153035 was able to significantly abrogate HB-EGF induction by EGF. The anti-erbB2 MAb L26 which interferes with heterodimer formation was able to block HB-EGF induction in response to EGF in MCF-10A cells and in the Ha-ras transformed cells only when used in combination with either the 225 MAb or PD153035. The MEK inhibitor PD90859 completely blocked EGF induction of HB-EGF mRNA levels in the nontransformed and Ha-ras transformed MCF-10A cells, which indicates that MAPK is involved in the signaling pathway of HB-EGF induction by EGF. An increase in the levels of HB-EGF may, therefore, be an important contributor to oncogenic transformation that is caused by Ha-ras overexpression in mammary epithelial cells. J. Cell. Physiol. 186:233-242, 2001. Published 2001 Wiley-Liss, Inc.
journal_name
J Cell Physioljournal_title
Journal of cellular physiologyauthors
Martínez-Lacaci I,De Santis M,Kannan S,Bianco C,Kim N,Wallace-Jones B,Wechselberger C,Ebert AD,Salomon DSdoi
10.1002/1097-4652(200002)186:2<233::AID-JCP1017>3.keywords:
subject
Has Abstractpub_date
2001-02-01 00:00:00pages
233-42issue
2eissn
0021-9541issn
1097-4652pii
10.1002/1097-4652(200002)186:2<233::AID-JCP1017>3.journal_volume
186pub_type
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