REVIEW

Cell Research, 15(4):237-246, Apr 2005

The role of epigenetic inactivation of 14-3-3¦Ä in human cancer

Dmitri LODYGIN, Heiko HERMEKING^*

Molecular Oncology, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried/Munich, Germany

Correspondence: Heiko Hermeking 001-49-(0)-89-8578-2875 (phone) 001-49-(0)-89-8578-2540 (fax) herme@biochem.mpg.de

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Abstract

Cancer cells show characteristic alterations in DNA methylation patterns. Aberrant CpG methylation of specific promoters results in inactivation of tumor suppressor genes and therefore plays an important role in carcinogenesis. The p53-regulated gene 14-3-3¦Ä undergoes frequent epigenetic silencing in several types of cancer, including carcinoma of the breast, prostate, and skin, suggesting that the loss of 14-3-3¦Ä expression may be causally involved in tumor progression. Functional studies demonstrated that 14-3-3¦Ä is involved in cell-cycle control and prevents the accumulation of chromosomal damage. The recent identification of novel 14-3-3¦Ä-associated proteins by a targeted proteomics approach implies that 14-3-3¦Ä regulates diverse cellular processes, which may become deregulated after silencing of 14-3-3¦Ä expression in cancer cells.

Keywords: 14-3-3¦Ä, CpG methylation, p53, epigenetic silencing, cancer, cell cycle.