Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer

K. A. Kwei, Y. H. Kim, L. Girard, J. Kao, M. Pacyna-Gengelbach, K. Salari, J. Lee, Y. L. Choi, M. Sato, P. Wang, T. Hernandez-Boussard, A. F. Gazdar, I. Petersen, J. D. Minna, J. R. Pollack

Research output: Contribution to journalArticle

157 Scopus citations

Abstract

Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic profiling of 128 lung cancer cell lines and tumors revealed frequent focal DNA amplification at cytoband 14q13.3, a locus not amplified in other tumor types. The smallest region of recurrent amplification spanned the homeobox transcription factor TITF1 (thyroid transcription factor 1; also called NKX2-1), previously linked to normal lung development and function. When amplified, TITF1 exhibited increased expression at both the RNA and protein levels. Small interfering RNA (siRNA)-mediated knockdown of TITF1 in lung cancer cell lines with amplification led to reduced cell proliferation, manifested by both decreased cell-cycle progression and increased apoptosis. Our findings indicate that TITF1 amplification and overexpression contribute to lung cancer cell proliferation rates and survival and implicate TITF1 as a lineage-specific oncogene in lung cancer.

Original languageEnglish (US)
Pages (from-to)3635-3640
Number of pages6
JournalOncogene
Volume27
Issue number25
DOIs
StatePublished - Jun 5 2008

Keywords

  • Genomic profiling
  • Lineage-specific oncogene
  • Lung cancer
  • NKX2-1
  • TITF1
  • TTF-1

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Kwei, K. A., Kim, Y. H., Girard, L., Kao, J., Pacyna-Gengelbach, M., Salari, K., Lee, J., Choi, Y. L., Sato, M., Wang, P., Hernandez-Boussard, T., Gazdar, A. F., Petersen, I., Minna, J. D., & Pollack, J. R. (2008). Genomic profiling identifies TITF1 as a lineage-specific oncogene amplified in lung cancer. Oncogene, 27(25), 3635-3640. https://doi.org/10.1038/sj.onc.1211012