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TIMP-1 inhibits apoptosis in breast carcinoma cells via a pathway involving pertussis toxin-sensitive G protein and c-Src

Title
TIMP-1 inhibits apoptosis in breast carcinoma cells via a pathway involving pertussis toxin-sensitive G protein and c-Src
Authors
Lee S.-J.Yoo H.J.Bae Y.S.Kim H.-J.Lee S.-T.
Ewha Authors
김화정배윤수
SCOPUS Author ID
김화정scopus; 배윤수scopus
Issue Date
2003
Journal Title
Biochemical and Biophysical Research Communications
ISSN
0006-291XJCR Link
Citation
vol. 312, no. 4, pp. 1196 - 1201
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
In addition to inhibiting matrix metalloproteinases, tissue inhibitor of metalloproteinase-1 (TIMP-1) is involved in the regulation of cell growth and survival. To determine its mechanism of action, we investigated effects of TIMP-1 on cell proliferation and survival and signaling pathways induced by TIMP-1 in the human breast carcinoma T-47D cell line. Treatment of T-47D cells with TIMP-1 strongly inhibited apoptosis induced by serum deprivation, but did not affect cell proliferation. TIMP-1 induced phosphorylation of Akt and extracellular signal-regulated protein kinases (ERKs), but pertussis toxin and specific inhibitors of Src family tyrosine kinases, protein tyrosine kinases, and phosphatidylinositol-3 kinase (PI3 kinase) blocked the ability of TIMP-1 to activate Akt and ERKs as well as the anti-apoptotic effect of TIMP-1. We found that TIMP-1 enhanced the kinase activities of c-Src and PI3 kinase and that this enhancement was inhibited by pertussis toxin. Inhibition of ERK activation, however, resulted in a slight decrease of the TIMP-1-induced anti-apoptotic effect. These findings demonstrate that the ability of TIMP-1 to inhibit apoptosis in T-47D cells is mediated by the sequential activation of pertussis toxin-sensitive G protein, c-Src, PI3 kinase, and Akt. © 2003 Elsevier Inc. All rights reserved.
DOI
10.1016/j.bbrc.2003.11.050
Appears in Collections:
약학대학 > 약학과 > Journal papers
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