Document Detail


Steroid receptor coactivator-3 expression in lung cancer and its role in the regulation of cancer cell survival and proliferation.
MedLine Citation:
PMID:  20663904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Steroid receptor coactivator-3 (SRC-3) is a histone acetyltransferase and nuclear hormone receptor coactivator, located on 20q12, which is amplified in several epithelial cancers and well studied in breast cancer. However, its possible role in lung cancer pathogenesis is unknown. We found SRC-3 to be overexpressed in 27% of non-small cell lung cancer (NSCLC) patients (n = 311) by immunohistochemistry, which correlated with poor disease-free (P = 0.0015) and overall (P = 0.0008) survival. Twenty-seven percent of NSCLCs exhibited SRC-3 gene amplification, and we found that lung cancer cell lines expressed higher levels of SRC-3 than did immortalized human bronchial epithelial cells (HBEC), which in turn expressed higher levels of SRC-3 than did cultured primary human HBECs. Small interfering RNA-mediated downregulation of SRC-3 in high-expressing, but not in low-expressing, lung cancer cells significantly inhibited tumor cell growth and induced apoptosis. Finally, we found that SRC-3 expression is inversely correlated with gefitinib sensitivity and that SRC-3 knockdown results in epidermal growth factor receptor tyrosine kinase inhibitor-resistant lung cancers becoming more sensitive to gefitinib. Taken together, these data suggest that SRC-3 may be an important oncogene and therapeutic target for lung cancer.
Authors:
Di Cai; David S Shames; Maria Gabriela Raso; Yang Xie; Young H Kim; Jonathan R Pollack; Luc Girard; James P Sullivan; Boning Gao; Michael Peyton; Meera Nanjundan; Lauren Byers; John Heymach; Gordon Mills; Adi F Gazdar; Ignacio Wistuba; Thomas Kodadek; John D Minna
Related Documents :
19124484 - Coexpression of alpha6beta4 integrin and guanine nucleotide exchange factor net1 identi...
24014594 - Circular rna and mir-7 in cancer.
15927524 - Survivin expression predicts poorer prognosis in patients with areca quid chewing-relat...
23387774 - Tissue mimicking materials for the detection of prostate cancer using shear wave elasto...
12442344 - Critical review of current treatment strategies for advanced hormone insensitive breast...
15583794 - Dendritic cells and hnscc: a potential treatment option? (review).
Publication Detail:
Type:  Journal Article     Date:  2010-07-27
Journal Detail:
Title:  Cancer research     Volume:  70     ISSN:  1538-7445     ISO Abbreviation:  Cancer Res.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-16     Completed Date:  2010-11-10     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  2984705R     Medline TA:  Cancer Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6477-85     Citation Subset:  IM    
Copyright Information:
(c)2010 AACR.
Affiliation:
Division of Translational Research, Hamon Center for Therapeutic Oncology Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antibodies, Monoclonal / pharmacology
Antineoplastic Agents / pharmacology
Carcinoma, Non-Small-Cell Lung / drug therapy,  enzymology*,  genetics,  pathology*
Cell Growth Processes / physiology
Cell Line, Tumor
Cell Survival / physiology
Disease-Free Survival
Drug Synergism
Gene Dosage
Gene Knockdown Techniques
Humans
Immunohistochemistry
Lung Neoplasms / drug therapy,  enzymology*,  genetics,  pathology*
Nuclear Receptor Coactivator 3 / antagonists & inhibitors,  biosynthesis*,  genetics
Protein Kinase Inhibitors / pharmacology
Quinazolines / pharmacology
RNA, Messenger / biosynthesis,  genetics
Receptor, Epidermal Growth Factor / antagonists & inhibitors,  metabolism
Signal Transduction
Grant Support
ID/Acronym/Agency:
DP1 OD000663-04/OD/NIH HHS
Chemical
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antineoplastic Agents; 0/Protein Kinase Inhibitors; 0/Quinazolines; 0/RNA, Messenger; EC 2.3.1.48/NCOA3 protein, human; EC 2.3.1.48/Nuclear Receptor Coactivator 3; EC 2.7.10.1/Receptor, Epidermal Growth Factor; PQX0D8J21J/cetuximab; S65743JHBS/gefitinib
Comments/Corrections

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


Previous Document:  A cancer detection platform which measures telomerase activity from live circulating tumor cells cap...
Next Document:  The human WRN and BLM RecQ helicases differentially regulate cell proliferation and survival after c...