Mice lacking a transcriptional corepressor Tob are predisposed to cancer

Tob is a member of antiproliferative family genes. Mice lacking tob are prone to spontaneous formation of tu-Mors. The occurrence rate of diethylnitrosamine-induced liver tumors is higher in tob(-/-) mice than in wildtype mice. tob(-/-)p53(-/-) mice show accelerated tumor formation in comparison with single null mice. Expression of cyclin D1 mRNA is increased in the absence of Tob and is reduced by Tob. Tob acts as a transcriptional corepressor and suppresses the cyclin D1 promoter activity through an interaction with histone deacetylase. Levels of tob mRNA are often decreased in human cancers, implicating tob in cancer development.