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Contribution of the Src family of kinases to the appearance of malignant phenotypes in renal cancer cells
Author(s) -
Yonezawa Yuko,
Nagashima Yoji,
Sato Hiromi,
Virgontiga,
Fukumoto Keiko,
Shirai Sumiko,
Hagiwara Hiromi,
Seki Taiichiro,
Ariga Toyohiko,
Senba Hironobu,
Suzuki Kazuyuki,
Asano Ryuji,
Hagiwara Kiyokazu,
Yano Tomohiro
Publication year - 2005
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20109
Subject(s) - proto oncogene tyrosine protein kinase src , biology , angiogenesis , cancer research , cancer , apoptosis , kinase , cancer cell , vascular endothelial growth factor , cell growth , microbiology and biotechnology , vegf receptors , biochemistry , genetics
Although the constitute activation of the Src family of kinases (Src) has been established as a poor prognostic factor in several types of cancer, the role of Src in renal cell carcinoma (RCC) has not been defined. This study aimed to determine whether Src could contribute to the appearance of malignant phenotypes in RCC. The role of Src in the appearance of malignant phenotypes in RCC was examined in two human renal cancer cell lines, Caki‐1 from human metastatic RCC and ACHN from human primary RCC. Src activity in Caki‐1 cells was higher than that in ACHN cells, and this difference corresponded to the difference of PP1 (a Src family inhibitor)‐induced cytotoxicity on the two cells. The difference in cytotoxicity between the cells did not depend on cell cycle regulation but on the induction of apoptosis, and the difference in apoptosis particularly related to the reduction of the Bcl‐xL level. Furthermore, in Caki‐1 cells with higher Src activity, Src stimulated the production of vascular endothelial growth factor (VEGF), partially via the activation of Stat3, and the inhibition of Src activity caused a reduction of the VEGF level in serum, angiogenesis, and tumor development in a xenograft model. These results suggested that Src contributed to the appearance of malignant phenotypes in renal cancer cells, particularly due to the resistance against apoptosis by Bcl‐xL and angiogenesis stimulated by Src‐Stat3‐VEGF signaling. © 2005 Wiley‐Liss, Inc.