Title |
Lineage-Specific Dependency of Lung Adenocarcinomas on the Lung Development Regulator TTF-1
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Published in |
Cancer Research, July 2007
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DOI | 10.1158/0008-5472.can-06-4774 |
Pubmed ID | |
Authors |
Hisaaki Tanaka, Kiyoshi Yanagisawa, Keiko Shinjo, Ayumu Taguchi, Ken Maeno, Shuta Tomida, Yukako Shimada, Hirotaka Osada, Takayuki Kosaka, Hideo Matsubara, Tetsuya Mitsudomi, Yoshitaka Sekido, Mitsune Tanimoto, Yasushi Yatabe, Takashi Takahashi |
Abstract |
Emerging evidence, although currently very sparse, suggests the presence of "lineage-specific dependency" in the survival mechanisms of certain cancers. TTF-1 has a decisive role as a master regulatory transcription factor in lung development and in the maintenance of the functions of terminal respiratory unit (TRU) cells. We show that a subset of lung adenocarcinoma cell lines expressing TTF-1, which presumably represent those derived from the TRU lineage, exhibit marked dependence on the persistent expression of TTF-1. The inhibition of TTF-1 by RNA interference (RNAi) significantly and specifically induced growth inhibition and apoptosis in these adenocarcinoma cell lines. Furthermore, a fraction of TTF-1-expressing tumors and cell lines displayed an increase in the gene dosage of TTF-1 in the analysis of 214 patients with non-small-cell lung cancer, including 174 adenocarcinomas, showing a tendency of higher frequency of increased gene copies at metastatic sites than at primary sites (P=0.07, by two-sided Fisher's exact test). These findings strongly suggest that in addition to the development and maintenance of TRU lineages in normal lung, sustained TTF-1 expression may be crucial for the survival of a subset of adenocarcinomas that express TTF-1, providing credence for the lineage-specific dependency model. |
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Geographical breakdown
Country | Count | As % |
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Japan | 1 | 2% |
United States | 1 | 2% |
Unknown | 51 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 10 | 19% |
Researcher | 10 | 19% |
Student > Doctoral Student | 4 | 8% |
Student > Master | 4 | 8% |
Student > Bachelor | 3 | 6% |
Other | 9 | 17% |
Unknown | 13 | 25% |
Readers by discipline | Count | As % |
---|---|---|
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Medicine and Dentistry | 13 | 25% |
Biochemistry, Genetics and Molecular Biology | 9 | 17% |
Unspecified | 1 | 2% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
Other | 1 | 2% |
Unknown | 14 | 26% |