Zhou Yong, Kato Hidenori, Asanoma Kazuo, Kondo Haruhiko, Arima Takahiro, Kato Kiyoko, Matsuda Takao, Wake Norio
Division of Molecular and Cell Therapeutics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, Oita, 874-0838, Japan.
Genomics. 2002 Nov;80(5):465-72.
We cloned the forkhead box C1 (FOXC1) gene, a member of the forkhead/winged-helix transcription factor family, as a transforming growth factor-beta1 (TGF-beta1) responsive gene. We showed that TGF-beta1 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-beta1 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-beta1 mediated signals.
我们克隆了叉头框C1（FOXC1）基因，它是叉头/翼状螺旋转录因子家族的一员，作为一种转化生长因子-β1（TGF-β1）反应基因。我们发现TGF-β1在几种人类癌细胞系中上调FOXC1的转录。在缺乏FOXC1等位基因两个拷贝的HeLa细胞中异位表达FOXC1 cDNA，可恢复TGF-β1通过将细胞阻滞在G0/G1期来抑制细胞生长的潜能。此外，对原发性子宫内膜癌和卵巢癌的筛查显示，其中6.7%存在FOXC1纯合缺失，1个FOXC1无义突变和1个错义突变，11.7%的原发性癌症存在转录沉默。相当一部分原发性癌症表现出体细胞突变的证据表明，FOXC1通过TGF-β1介导的信号发挥肿瘤抑制作用。
