Attenuation of the expression of the focal adhesion kinase induces apoptosis in tumor cells.
The focal adhesion kinase (FAK) is a nonreceptor protein tyrosine kinase implicated in integrin-mediated signal transduction pathways, oncogenic transformation by v-src, and the invasion of human tumors. The overexpression of p125FAK in a variety of human tumors and tumor cell lines in comparison to their nontransformed counterparts suggested that attenuation of p125FAK expression might have an effect on tumor cell proliferation. In this study, we have treated tumor cell lines that expressed high levels of p125FAK with different antisense oligonucleotides to FAK, and have specifically attenuated p125FAK expression. The cells treated with antisense oligonucleotides not only lost their attachment, but also underwent apoptosis. Extensive control oligonucleotide experiments suggested that this attenuation was highly FAK specific. Furthermore, normal human fibroblasts, which did not express high levels of p125FAK, did not lose their attachment or become apoptotic with FAK antisense treatment. These results suggested that FAK is involved in adhesion-mediated growth in tumor cells and that FAK may be a rational gene-directed target for disrupting tumor cell growth.
Xu
L H
LH
Department of Surgery, University of North Carolina at Chapel Hill, School of Medicine, USA.
Owens
L V
LV
Sturge
G C
GC
Yang
X
X
Liu
E T
ET
Craven
R J
RJ
Cance
W G
WG
D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D016376:Oligonucleotides, Antisense; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human