Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1

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

Research output: Contribution to journalArticle

149 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)6007-6011
Number of pages5
JournalCancer Research
Volume67
Issue number13
DOIs
Publication statusPublished - Jul 1 2007

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Adenocarcinoma
Maintenance
Cell Line
Lung
Gene Dosage
Survival
RNA Interference
Tumor Cell Line
Gene Frequency
Non-Small Cell Lung Carcinoma
Transcription Factors
Apoptosis
Growth
Adenocarcinoma of lung
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Tanaka, H., Yanagisawa, K., Shinjo, K., Taguchi, A., Maeno, K., Tomida, S., ... Takahashi, T. (2007). Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1. Cancer Research, 67(13), 6007-6011. https://doi.org/10.1158/0008-5472.CAN-06-4774

Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1. / Tanaka, Hisaaki; Yanagisawa, Kiyoshi; Shinjo, Keiko; Taguchi, Ayumu; Maeno, Ken; Tomida, Shuta; Shimada, Yukako; Osada, Hirotaka; Kosaka, Takayuki; Matsubara, Hideo; Mitsudomi, Tetsuya; Sekido, Yoshitaka; Tanimoto, Mitsune; Yatabe, Yasushi; Takahashi, Takashi.

In: Cancer Research, Vol. 67, No. 13, 01.07.2007, p. 6007-6011.

Research output: Contribution to journalArticle

Tanaka, H, Yanagisawa, K, Shinjo, K, Taguchi, A, Maeno, K, Tomida, S, Shimada, Y, Osada, H, Kosaka, T, Matsubara, H, Mitsudomi, T, Sekido, Y, Tanimoto, M, Yatabe, Y & Takahashi, T 2007, 'Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1', Cancer Research, vol. 67, no. 13, pp. 6007-6011. https://doi.org/10.1158/0008-5472.CAN-06-4774
Tanaka, Hisaaki ; Yanagisawa, Kiyoshi ; Shinjo, Keiko ; Taguchi, Ayumu ; Maeno, Ken ; Tomida, Shuta ; Shimada, Yukako ; Osada, Hirotaka ; Kosaka, Takayuki ; Matsubara, Hideo ; Mitsudomi, Tetsuya ; Sekido, Yoshitaka ; Tanimoto, Mitsune ; Yatabe, Yasushi ; Takahashi, Takashi. / Lineage-specific dependency of lung adenocarcinomas on the lung development regulator TTF-1. In: Cancer Research. 2007 ; Vol. 67, No. 13. pp. 6007-6011.
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