Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progression

doi:10.1073/pnas.0710091104

Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progression

*Molecular Oncology Group, McGill University, Royal Victoria Hospital, Room H5.21, 687 Pine Avenue West, Montreal, QC, Canada H3A 1A1;
^§Departments of Biochemistry and Medicine, McGill University, McIntyre Medical Building, Room 802, 3655 Promenade Sir William Osler, Montreal, QC, Canada H3G 1Y6;
^†Center for Comparative Medicine, University of California, County Road 98 and Hutchison Drive, Davis, CA 95616; and
^‡The Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Bearsden, Glasgow G61 1BD, United Kingdom

Communicated by Richard O. Hynes, Massachusetts Institute of Technology, Cambridge, MA, October 24, 2007 (received for review June 2, 2007)

Abstract

Elevated expression and activation of the focal adhesion kinase (FAK) occurs in a large proportion of human breast cancers. Although several studies have implicated FAK as an important signaling molecule in cell culture systems, evidence supporting a role for FAK in mammary tumor progression is lacking. To directly assess the role of FAK in this process, we have used the Cre/loxP recombination system to disrupt FAK function in the mammary epithelium of a transgenic model of breast cancer. Using this approach, we demonstrate that FAK expression is required for the transition of premalignant hyperplasias to carcinomas and their subsequent metastases. This dramatic block in tumor progression was further correlated with impaired mammary epithelial proliferation. These observations provide direct evidence that FAK plays a critical role in mammary tumor progression.

Footnotes

^¶To whom correspondence should be addressed. E-mail: william.muller{at}mcgill.ca
Author contributions: H.L. and W.J.M. designed research; H.L., V.S.-G., D.Z., and R.D.C. performed research; R.D.C., G.W.M., and M.C.F. contributed new reagents/analytic tools; H.L., V.S.-G., and W.J.M. analyzed data; and H.L. and W.J.M. wrote the paper.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0710091104/DC1.
Freely available online through the PNAS open access option.