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

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 t...

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Bibliographic Details
Published in:Genes & development 2004-12, Vol.18 (24), p.2998-3003
Main Authors: McLean, Gordon W, Komiyama, Noboru H, Serrels, Bryan, Asano, Hidefumi, Reynolds, Louise, Conti, Francesco, Hodivala-Dilke, Kairbaan, Metzger, Daniel, Chambon, Pierre, Grant, Seth G N, Frame, Margaret C
Format: Article
Language:English
Subjects:
9,10-Dimethyl-1,2-benzanthracene - toxicity
Animals
Apoptosis - genetics
Apoptosis - physiology
Blotting, Western
DNA Primers
Flow Cytometry
Fluorescent Antibody Technique
Focal Adhesion Kinase 1
Focal Adhesion Protein-Tyrosine Kinases
Gene Deletion
Genetics
Genotype
Hydroxytestosterones - metabolism
Immunohistochemistry
Integrases - metabolism
Keratin-14
Keratinocytes - physiology
Keratins - metabolism
Life Sciences
Mice
Mice, Transgenic
Neoplasm Metastasis - genetics
Neoplasm Metastasis - prevention & control
Protein-Tyrosine Kinases - genetics
Receptors, Estrogen - metabolism
Research Communications
Skin Neoplasms - chemically induced
Skin Neoplasms - genetics
Tamoxifen - analogs & derivatives
Tamoxifen - metabolism
Tamoxifen - pharmacology
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Summary: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.
ISSN:0890-9369
1549-5477
DOI:10.1101/gad.316304