Functional involvement of src and focal adhesion kinase in a CD99 splice variant-induced motility of human breast cancer cells.
Earlier report showed that expression of a splice variant of CD99 transmembrane protein increases invasive ability of human breast cancer cells. Cell motility was also significantly enhanced by the CD99 splice variant expression. In an effort to identify the cellular components that mediate a signal transduction pathway triggered by the CD99 splice variant, known signal path inhibitors were examined for their effects on the motility of the CD99 splice variant-transfected MDA-MB-231 breast cancer cells. Phenylarsine oxide, an inhibitor of phosphatase specific for focal adhesion kinase, and PP1, an inhibitor of src kinase family, significantly suppressed motility of the cells. Among different types of src transfectant clones generated, kinase-negative mutant src transfectant cells were 80% less motile than the mock cells transfected with an empty-vector, while v-src and c-src transfectants exhibited cell motility levels at or slightly above the mock transfectant. These results suggest that src and focal adhesion kinase mediate the intracellular signaling pathway of a CD99 splice variant for the induction of motility of human breast cancer cells.
Lee
Hyuk-Joon
HJ
Vascular System Research Center, Division of Life Sciences, College of Natural Sciences, Kangwon National University, Chunchon 200-701, Korea.
Kim
Eunsook
E
Jee
Bokeun
B
Hahn
Jang-Hee
JH
Han
Kyuhyoung
K
Jung
Kyeong Cheon
KC
Park
Seong Hoe
SH
Lee
Hansoo
H
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000235:genetics*; D001152:Arsenicals / Q000494:pharmacology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002465:Cell Movement / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases; D015870:Gene Expression; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000071443:12E7 Antigen; C108123:4-amino-5-(4-methylphenyl)-7-(tert-butyl)pyrazolo(3,4-d)pyrimidine; D015703:Antigens, CD; D001152:Arsenicals; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D011720:Pyrazoles; D011743:Pyrimidines; C029341:oxophenylarsine; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019061:src-Family Kinases