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    
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.
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
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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:  2014-08-25    
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.
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MeSH Terms
Antibodies, Monoclonal / pharmacology
Antibodies, Monoclonal, Humanized
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
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
DP1 OD000663/OD/NIH HHS; DP1 OD000663-04/OD/NIH HHS
Reg. No./Substance:
0/Antibodies, Monoclonal; 0/Antibodies, Monoclonal, Humanized; 0/Antineoplastic Agents; 0/Protein Kinase Inhibitors; 0/Quinazolines; 0/RNA, Messenger; EC protein, human; EC Receptor Coactivator 3; EC, Epidermal Growth Factor; PQX0D8J21J/cetuximab; S65743JHBS/gefitinib

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