The transcription factor ITF-2A induces cell cycle arrest via p21Cip1

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.