The transcription factor ITF-2A induces cell cycle arrest via p21(Cip1).
The transcription factor ITF-2A induces cell cycle arrest via p21(Cip1).
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DOI：
10.1016/j.bbrc.2009.07.102
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发表时间：
2009-10
影响因子：
3.1
通讯作者：
A. Herbst;Simone Helferich;A. Behrens;B. Göke;F. Kolligs
中科院分区：
文献类型：
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作者：
A. Herbst;Simone Helferich;A. Behrens;B. Göke;F. Kolligs
杂合性缺失（LOH）是癌症的一个标志，结直肠癌中染色体区域5q、8p、17p和18q常受LOH影响。ITF2基因位于染色体18q上，我们最近证明碱性螺旋-环-螺旋（bHLH）转录因子ITF-2B的表达受到LOH的影响。除ITF-2B外，ITF2基因还编码缺乏ITF-2B中氨基末端序列的同种异构体ITF-2A。分析微解剖结直肠肿瘤组织中ITF-2A的表达，发现ITF-2A在结直肠癌中经常表达缺失，提示ITF-2A的缺失为癌细胞提供了生长优势。进一步的研究表明，结肠癌细胞系中ITF-2A的重新表达会干扰细胞周期的进展。这些数据支持了染色体18q上的ITF2基因是肿瘤抑制基因的观点。
Loss of heterozygosity (LOH) is a hallmark of cancer and the chromosomal regions 5q, 8p, 17p, and 18q are frequently affected by LOH in colorectal cancer. The ITF2 gene is located on chromosome 18q and we have recently demonstrated that expression of the basic helix-loop-helix (bHLH) transcription factor ITF-2B is affected by LOH. Apart from ITF-2B, the ITF2 gene also encodes the isoform ITF-2A that lacks amino-terminal sequences found in ITF-2B. Analysis of ITF-2A expression in micro-dissected colorectal tumor tissue revealed that ITF-2A expression is frequently lost in colorectal cancers, suggesting that loss of ITF-2A provides cancer cells with a growth advantage. Further studies demonstrated that re-expression of ITF-2A in colon cancer cell lines interferes with cell cycle progression. This data support the notion that the ITF2 gene on chromosome 18q is a tumor suppressor gene.