Specific deletion of focal adhesion kinase suppresses tumor formation and blocks malignant progression.

Abstract	We have generated mice with a floxed fak allele under the control of keratin-14-driven Cre fused to a modified estrogen receptor (CreER(T2)). 4-Hydroxy-tamoxifen treatment induced fak deletion in the epidermis, and suppressed chemically induced skin tumor formation. Loss of fak induced once benign tumors had formed inhibited malignant progression. Although fak deletion was associated with reduced migration of keratinocytes in vitro, we found no effect on wound re-epithelialization in vivo. However, increased keratinocyte cell death was observed after fak deletion in vitro and in vivo. Our work provides the first experimental proof implicating FAK in tumorigenesis, and this is associated with enhanced apoptosis.
Authors	Gordon W McLean, Noboru H Komiyama, Bryan Serrels, Hidefumi Asano, Louise Reynolds, Francesco Conti, Kairbaan Hodivala-Dilke, Daniel Metzger, Pierre Chambon, Seth G N Grant, Margaret C Frame
Journal	Genes & development (Genes Dev) Vol. 18 Issue 24 Pg. 2998-3003 (Dec 15 2004) ISSN: 0890-9369 [Print] United States
PMID	15601818 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	DNA Primers Hydroxytestosterones Keratin-14 Krt14 protein, mouse Receptors, Estrogen Tamoxifen afimoxifene 4,17 beta-dihydroxy-4-androstene-3-one 9,10-Dimethyl-1,2-benzanthracene Keratins Protein-Tyrosine Kinases Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Ptk2 protein, mouse Cre recombinase Integrases
Topics	9,10-Dimethyl-1,2-benzanthracene (toxicity) Animals Apoptosis (genetics, physiology) Blotting, Western DNA Primers Flow Cytometry Fluorescent Antibody Technique Focal Adhesion Kinase 1 Focal Adhesion Protein-Tyrosine Kinases Gene Deletion Genotype Hydroxytestosterones (metabolism) Immunohistochemistry Integrases (metabolism) Keratin-14 Keratinocytes (physiology) Keratins (metabolism) Mice Mice, Transgenic Neoplasm Metastasis (genetics, prevention & control) Protein-Tyrosine Kinases (genetics) Receptors, Estrogen (metabolism) Skin Neoplasms (chemically induced, genetics) Tamoxifen (analogs & derivatives, metabolism, pharmacology)

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