Journal Article

Role of Raf-1 and FAK in cell density-dependent regulation of integrin-dependent activation of MAP kinase

Lianfeng Zhang, Mary Bewick and Robert M. Lafrenie

in Carcinogenesis

Volume 23, issue 7, pages 1251-1258
Published in print July 2002 | ISSN: 0143-3334
Published online July 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.7.1251
Role of Raf-1 and FAK in cell density-dependent regulation of integrin-dependent activation of MAP kinase

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MAP kinase can be activated by integrin-dependent adhesion in a FAK-dependent manner. Cell–cell contact inhibition is continuously active in controlling cell growth and the loss of cell–cell contact inhibition is correlated with the malignant characteristics of cancer cells. In this study we showed that cell adhesion to fibronectin for 1 h activated MAP kinase phosphorylation. However, when non-tumorigenic HSG cells, MCF-10A cells, or 293 cells were plated on fibronectin-coated substrates for 1 h at high cell density (which favors cell–cell contact), MAP kinase phosphorylation was not enhanced. Tumorigenic breast cancer cells, BT474, Cama, MCF-7, MDA-MB-231 and SKBR3, did not show inhibition of MAP kinase phosphorylation but rather enhanced MAP kinase phosphorylation when cultured at high density on fibronectin-coated substrates. Adhesion of HSG cells to fibronectin also increased FAK phosphorylation and this FAK phosphorylation was partially inhibited when cells were cultured at high density. Expression of Raf-1 catalytic domain-GFP in HSG cells could overcome the cell density-dependent inhibition of MAP kinase phosphorylation and FAK phosphorylation. The expression of Raf-1-catalytic domain-GFP also upregulated the expression of αv integrin and promoted cell–cell adhesion in HSG cells. These results suggest that the active form of Raf-1 may interrupt cell–cell contact inhibition by promoting αv integrin expression, which has been implicated in cell aggregation.

Keywords: DMEM, Dulbecco's modified essential medium; FCS, fetal calf serum

Journal Article.  6566 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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