Mice lacking a transcriptional corepressor Tob are predisposed to cancer
- Yutaka Yoshida1,8,
- Takahisa Nakamura1,8,
- Masato Komoda4,
- Hitoshi Satoh2,
- Toru Suzuki1,
- Junko K. Tsuzuku1,
- Takashi Miyasaka1,
- Eri H. Yoshida1,
- Hisashi Umemori1,
- Reiko K. Kunisaki3,
- Kenzaburo Tani4,
- Shunsuke Ishii5,
- Shigeo Mori2,
- Masami Suganuma4,
- Tetsuo Noda6,7, and
- Tadashi Yamamoto1,9
- Divisions of 1Oncology, 2Pathology, and 3Molecular Therapy, The Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; 4Saitama Cancer Center, Saitama 362-0806, Japan; 5Laboratory of Molecular Genetics, Tsukuba Life Science Center, RIKEN, Tsukuba, Ibaraki 305-0074, Japan; 6Department of Cell Biology, Cancer Institute, Toshima-ku, Tokyo 170-8455, Japan; 7Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai 980-8575, Japan
Abstract
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 intob −/− 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.
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Footnotes
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↵8 These authors contributed equally to this work.
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↵9 Corresponding author.
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E-MAIL tyamamot{at}ims.u-tokyo.ac.jp; FAX 81-3-5449-5413.
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1088003.
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- Received February 22, 2003.
- Accepted April 2, 2003.
- Cold Spring Harbor Laboratory Press
