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A more recent version of this article appeared on December 6, 2002
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M207986200v1
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Papers In Press, published online ahead of print October 8, 2002
J. Biol. Chem, 10.1074/jbc.M207986200
Submitted on August 6, 2002
Revised on October 8, 2002
Accepted on October 8, 2002

Transcriptional activation of the MUC2 gene by p53

Keizou Ookawa, Toshihiro Kudo, Shu Aizawa, Hiroshi Saito, and Shigeki Tsuchida

Second Department of Biochemistry, Hirosaki University School of Medicine, Hirosaki, Aomori 036-8562

Corresponding Author: kookawa{at}cc.hirosaki-u.ac.jp

MUC2 is one of the major components of mucins that provide a protective barrier between epithelial surfaces and the gut lumen. We investigated possible alterations of MUC2 gene expression by p53 and p21sdi1/waf1/cip1 in a human colon cancer cell line, DLD-1, establishing subclones in which a tetracycline-regulatable promoter controls exogenous p53 and p21 expression. MUC2 mRNA more significantly increased in response to p53 than to p21. Unexpectedly, MUC2 expression was also induced in human osteosarcoma cells, U-2OS and Saos-2, by exogenous p53. We next performed a reporter assay to test the direct regulation of the MUC2 gene expression by p53. Deletion and mutagenesis of the MUC2 promoter region showed that it contains two sites for trans-activation by p53. Furthermore, an electrophoretic mobility shift assay indicated that p53 binds to those elements. We analyzed MUC2 expression in other cell types possessing a functional p53 after exposure to various forms of stress. In MCF7 breast cancer and A427 lung cancer cells, MUC2 expression was increased along with the endogenous p53 level by actinomycin D, UVC and X-ray, but not in RERF-LC-MS lung cancer cells carrying a mutated p53. These results suggest that p53 directly activates the MUC2 gene in many cell types.


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