Identification of FOXC1 as a TGF-β1 responsive gene and its involvement in negative regulation of cell growth

Yong Zhou, Hidenori Kato, Kazuo Asanoma, Haruhiko Kondo, Takahiro Arima, Kiyoko Kato, Takao Matsuda, Norio Wake

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We cloned the forkhead box C1 (FOXC1) gene, a member of the forkhead/winged-helix transcription factor family, as a transforming growth factor-β1 (TGF-β1) responsive gene. We showed that TGF-β1 upregulated transcription of FOXC1 in several human cancer cell lines. Ectopic expression of FOXC1 cDNA in HeLa cells, which lack both copies of the FOXC1 allele, restores the potential of TGF-β1 to inhibit cell growth by arresting cells in the G0/G1 phase. In addition, screens of primary endometrial and ovarian cancers revealed homozygous deletion of FOXC1 in 6.7% of them, one nonsense and one missense mutation of FOXC1, and transcriptional silencing in 11.7% of primary cancers. Evidence that a significant fraction of primary cancers exhibited somatic mutations suggests that FOXC1 functions as a tumor suppressor through TGF-β1 mediated signals.

元の言語英語
ページ(範囲)465-472
ページ数8
ジャーナルGenomics
80
発行部数5
DOI
出版物ステータス出版済み - 1 1 2002

All Science Journal Classification (ASJC) codes

  • Genetics

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