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Hyperphosphorylation of Retinoblastoma Protein and p53 by Okadaic Acid, a Tumor Promoter¹

Cancer Prevention Division, National Cancer Center Research Institute, Tokyo 104, Japan

² To whom requests for reprints should be addressed.

A potent tumor promoter, okadaic acid, induced hyperphosphorylation of tumor suppressor proteins, retinoblastoma protein and p53, by in vitro incubation with nuclei isolated from rat regenerating liver as well as by incubation with primary human fibroblasts. Most of the retinoblastoma protein migrated to a hyperphosphorylated position in electrophoresis. The phosphorylation of p53 was increased at a rate 8 times that in non-treated primary human fibroblasts. Hyperphosphorylation of tumor suppressor proteins, mediated through inhibition of protein phosphatases 1 and 2A, is involved in tumor promotion by okadaic acid. The significance of hyperphosphorylation of the retinoblastoma protein and p53 is discussed in relation to the regulation of the cell cycle.

¹ This work was supported in part by Grants-in-Aid for Cancer Research from the Ministry of Education, Science, and Culture; a grant from the Ministry of Health and Welfare for a Comprehensive 10-Year Strategy for Cancer Control, Japan; and grants from the Foundation for Promotion of Cancer Research, the Uehara Memorial Life Science Foundation, and the Princess Takamatsu Cancer Research Fund.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 11/ 2/92. Accepted 11/30/92.

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