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Regulation of the expression of c-Myc by β1 integrins in epithelial cells

Oncogene volume 20, pages 759–768 (2001)Cite this article

Abstract

Cell adhesion promotes cellular proliferation through the regulation of gene expression, including the immediate early genes. However, the precise role of cell adhesion in the regulation of the c-Myc proto-oncogene is not clear, and the adhesion-dependent signaling pathway(s) regulating the expression of c-Myc has yet to be defined. We now show that integrin signaling directly regulates the expression of c-Myc in the mammary epithelial cell line 184A1N4 (A1N4). Adhesion of quiescent A1N4 cells to fibronectin, and to collagen types IV or I, induces the expression of c-Myc in an ECM concentration-dependent fashion. Cytoskeletal rearrangement, and integrin engagement and integrin clustering are required for the induction of c-Myc by fibronectin. Furthermore, β1 integrin function-blocking antibodies prevent the adhesion-dependent induction of c-Myc. Adhesion of A1N4 cells results in the activation both of c-Src and of the Erk 1/2 mitogen-activated protein kinase (MAPK), each of which precedes the induction of c-Myc. Pharmacological inhibitors specific for either the c-Src family of kinases or for MEK1 block the adhesion-dependent induction of c-Myc. These observations indicate that β1 integrins regulate the expression of c-Myc through the activation of the Src family of tyrosine kinases and the MAK kinase pathway.

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Acknowledgements

This work was supported by DOD BC961668 fellowship to CM Benaud and NIH R01AG1496 to RB Dickson.

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Authors and Affiliations

  1. Vincent T Lombardi Cancer Center, Georgetown University Medical Center, 3970 Reservoir Rd., NW, 20007, Washington DC, USA

    Christelle M Benaud & Robert B Dickson

  2. Department of Cell Biology, Georgetown University Medical Center, 3970 Reservoir Rd., NW, 20007, Washington DC, USA

    Christelle M Benaud & Robert B Dickson

  3. Department of Pharmacology, Georgetown University Medical Center, 3970 Reservoir Rd., NW, 20007, Washington DC, USA

    Robert B Dickson

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Benaud, C., Dickson, R. Regulation of the expression of c-Myc by β1 integrins in epithelial cells. Oncogene 20, 759–768 (2001). https://doi.org/10.1038/sj.onc.1204152

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