Mice lacking a transcriptional corepressor Tob are predisposed to cancer

• Published in: Genes & development 2003-05, Vol.17 (10), p.1201-1206
• Main Authors: Yoshida, Yutaka, Nakamura, Takahisa, Komoda, Masato, Satoh, Hitoshi, Suzuki, Toru, Tsuzuku, Junko K, Miyasaka, Takashi, Yoshida, Eri H, Umemori, Hisashi, Kunisaki, Reiko K, Tani, Kenzaburo, Ishii, Shunsuke, Mori, Shigeo, Suganuma, Masami, Noda, Tetsuo, Yamamoto, Tadashi
• Format: Article
• Language: English
• Subjects: Animals; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cyclin D1 - genetics; Cyclin D1 - metabolism; Fibroblasts - metabolism; Genes, Tumor Suppressor; Genetic Predisposition to Disease; Histone Deacetylases - metabolism; Humans; Intracellular Signaling Peptides and Proteins; Mice; Neoplasms, Experimental - etiology; Neoplasms, Experimental - genetics; Promoter Regions, Genetic; Research Communication; RNA, Messenger - metabolism; Transcription, Genetic; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Proteins
• ISSN: 0890-9369; 1549-5477
• DOI: 10.1101/gad.1088003

tob is a member of antiproliferative family genes. Mice lacking tob are prone to spontaneous formation of tumors. The occurrence rate of diethylnitrosamine-induced liver tumors is higher in tob(-/-) mice than in wild-type 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.