This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yoon, S.-O. Articles by Mercurio, A. M. Search for Related Content PubMed PubMed Citation Articles by Yoon, S.-O. Articles by Mercurio, A. M.

Ras Stimulation of E2F Activity and a Consequent E2F Regulation of Integrin ₆ß₄ Promote the Invasion of Breast Carcinoma Cells

Division of Cancer Biology and Angiogenesis, Department of Pathology Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts

Requests for reprints: Arthur M. Mercurio, Department of Cancer Biology, University of Massachusetts Medical School, LRB-408, 364 Plantation Street, Worcester, MA 01605. Phone: 508-856-8676; Fax: 508-856-1310; E-mail: arthur.mercurio{at}umassmed.edu.

Active Ras proteins contribute to breast carcinogenesis and progression. Here, we provide evidence that active H-Ras regulates the expression and activity of the E2F family of transcription factors in SUM-159 breast carcinoma cells. In addition, we show by using a DNA-binding mutant of E2F, as well as expression of specific E2Fs that are transcriptionally active, that the active E2Fs1-3 can mediate the H-Ras-dependent invasion of SUM-159 cells. The inhibitory E2Fs4-5, in contrast, do not influence invasion. One mechanism by which the active E2Fs promote H-Ras-dependent invasion seems to be their ability to increase expression of the ß₄ integrin subunit, a component of the ₆ß₄ integrin that is known to enhance carcinoma invasion. Specifically, expression of E2Fs1-3 increased ß₄ mRNA, protein, and cell surface expression. The active E2Fs were unable to stimulate invasion in cells that expressed a ß₄ short hairpin RNA. This effect of the active E2Fs on ß₄ expression does not seem to result from E2F-mediated ß₄ transcription because the ß₄ promoter lacks known E2F binding motifs. In summary, the data reported here indicate a novel mechanism by which H-Ras can promote the invasion of breast carcinoma cells. This mechanism links active H-Ras, transcriptionally active E2F, and the ₆ß₄ integrin in a common pathway that culminates in enhanced ₆ß₄-dependent invasion. (Cancer Res 2006; 66(12): 6288-95)

This article has been cited by other articles:

				T. H. Kim, H. I. Kim, Y. H. Soung, L. A. Shaw, and J. Chung Integrin ({alpha}6{beta}4) Signals Through Src to Increase Expression of S100A4, a Metastasis-Promoting Factor: Implications for Cancer Cell Invasion Mol. Cancer Res., October 1, 2009; 7(10): 1605 - 1612. [Abstract] [Full Text] [PDF]

				N. Skuli, S. Monferran, C. Delmas, G. Favre, J. Bonnet, C. Toulas, and E. Cohen-Jonathan Moyal {alpha}v{beta}3/{alpha}v{beta}5 Integrins-FAK-RhoB: A Novel Pathway for Hypoxia Regulation in Glioblastoma Cancer Res., April 15, 2009; 69(8): 3308 - 3316. [Abstract] [Full Text] [PDF]

				M. Chen, M. Sinha, B. A. Luxon, A. R. Bresnick, and K. L. O'Connor Integrin {alpha}6{beta}4 Controls the Expression of Genes Associated with Cell Motility, Invasion, and Metastasis, Including S100A4/Metastasin J. Biol. Chem., January 16, 2009; 284(3): 1484 - 1494. [Abstract] [Full Text] [PDF]

				R. Blum, R. Elkon, S. Yaari, A. Zundelevich, J. Jacob-Hirsch, G. Rechavi, R. Shamir, and Y. Kloog Gene Expression Signature of Human Cancer Cell Lines Treated with the Ras Inhibitor Salirasib (S-Farnesylthiosalicylic Acid) Cancer Res., April 1, 2007; 67(7): 3320 - 3328. [Abstract] [Full Text] [PDF]