Document Detail

p190A RhoGAP is involved in EGFR pathways and promotes proliferation, invasion and migration in lung adenocarcinoma cells.
MedLine Citation:
PMID:  24043274     Owner:  NLM     Status:  In-Data-Review    
Overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‑TKIs) is an emerging issue in lung cancer treatment. We report evidence that a GTPase-activating protein, p190-A RhoGAP (p190), is a potential molecular target for the treatment of lung adenocarcinoma. We documented inhibition of phosphorylation of p190 by EGFR-TKI treatment in lung adenocarcinoma cell lines. Small interfering RNA-mediated knockdown of p190 leads lung adenocarcinoma cells to growth suppression and to inhibition of invasion/migration through inducing cell cycle arrest but not apoptosis. These findings were observed not only in EGFR-TKI-sensitive cells but also in EGFR-TKI-resistant cells; even in cell lines harboring K-ras mutations. The mechanism of this inhibitory effect on growth and invasion/migration was Ras inactivation through disrupting the p190-A RhoGAP/p120RasGAP complex. In addition, a high level of p190 mRNA expression was observed in majority of surgically obtained tissue from lung adenocarcinoma patients. Overexpression of p190 mRNA associated with poor disease-free survival. The results suggest that overexpression of p190 mRNA may be involved in the carcinogenesis of lung adenocarcinoma. These findings indicate that p190 is a possible molecular target for treatment of lung adenocarcinoma.
Hirotsugu Notsuda; Akira Sakurada; Chiaki Endo; Yoshinori Okada; Akira Horii; Hiroshi Shima; Takashi Kondo
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Publication Detail:
Type:  Journal Article     Date:  2013-09-13
Journal Detail:
Title:  International journal of oncology     Volume:  43     ISSN:  1791-2423     ISO Abbreviation:  Int. J. Oncol.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-09-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9306042     Medline TA:  Int J Oncol     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  1569-77     Citation Subset:  IM    
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
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