Steroid receptor coactivator-3 expression in lung cancer and its role in the regulation of cancer cell survival and proliferation

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

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Steroid receptor coactivator-3 (SRC-3) is a histone acetyltransferase and nuclear hormone receptor co-activator, 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.

Original languageEnglish (US)
Pages (from-to)6477-6485
Number of pages9
JournalCancer Research
Volume70
Issue number16
DOIs
Publication statusPublished - Aug 15 2010

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

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