期刊
ONCOGENE
卷 27, 期 25, 页码 3635-3640出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1211012
关键词
TITF1; lineage-specific oncogene; genomic profiling; lung cancer; TTF-1; NKX2-1
资金
- NCI NIH HHS [P50 CA070907-10, T32 CA09151, T32 CA009151, P50 CA070907, R01 CA97139, P50CA70907, R01 CA097139, R01 CA097139-02, T32 CA009151-31, P50 CA070907-11] Funding Source: Medline
Lung cancer is a leading cause of cancer death, where the amplification of oncogenes contributes to tumorigenesis. Genomic pro. ling 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.
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