Mammary epithelial-specific disruption of the focal adhesion kinase blocks mammary tumor progression.
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.
Molecular Oncology Group, McGill University, Royal Victoria Hospital, Room H5.21, 687 Pine Avenue West, Montreal, QC, Canada H3A 1A1.
Hicham
H
Lahlou
Virginie
V
Sanguin-Gendreau
Dongmei
D
Zuo
Robert D
RD
Cardiff
Gordon W
GW
McLean
Margaret C
MC
Frame
William J
WJ
Muller
D000818:Animals; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics / Q000556:secondary*; D018450:Disease Progression; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D017353:Gene Deletion; D008175:Lung Neoplasms / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic
D051416:Focal Adhesion Protein-Tyrosine Kinases