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    
Abstract/OtherAbstract:
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.
Authors:
Hirotsugu Notsuda; Akira Sakurada; Chiaki Endo; Yoshinori Okada; Akira Horii; Hiroshi Shima; Takashi Kondo
Related Documents :
23679684 - Effects of celecoxib treatment over the akt pathway in head and neck squamous cell carc...
23599754 - Repression of dicer is associated with invasive phenotype and chemoresistance in ovaria...
24474764 - Circadian rhythms synchronize mitosis in neurospora crassa.
25086604 - A carbon nanotube-polymer composite for t-cell therapy.
9145534 - Spectroscopic analysis of the cytoagglutinating activity of abrin-b isolated from abrus...
24250774 - Correction: telomere reprogramming and maintenance in porcine ips cells.
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    
Affiliation:
Department of Thoracic Surgery, Institute of Development, Aging and Cancer, Tohoku University, Sendai 980-8575, Japan.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Haemolysis: the harbinger of recurrent mitral regurgitation after mitral valve repair.
Next Document:  Bullied Children and Psychosomatic Problems: A Meta-analysis.