Oncogene. 2005 Dec 5; [Epub ahead of print]
The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth
Bernard D, Gil J, Dumont P, Rizzo S, Monte D, Quatannens B, Hudson D, Visakorpi T, Fuks F, de Launoit Y.
1Molecular Virology Laboratory, Free University of Brussels, Brussels, Belgium.
Abstract
The incidence of prostate cancer is increasing in western countries because of population aging. Prostate cancer begins as an androgen-dependent disease, but it can become androgen independent at a later stage or in tumors recurring after an antihormonal treatment. Although many genetic events have been described to be involved in androgen-dependent and/or -independent prostate cancer growth, little is known about the contribution of epigenetic events. Here we have examined the possibility that the methyl-CpG-binding protein MECP2 might play a role in controlling the growth of prostate cancer cells. Inhibition of MECP2 expression by stable short hairpin RNA stopped the growth of both normal and cancer human prostate cells. In addition, ectopic expression of the MECP2 conferred a growth advantage to human prostate cancer cells. More importantly, this expression allowed androgen-dependent cells to grow independently of androgen stimulation and to retain tumorigenic properties in androgen-depleted conditions. Analysis of signaling pathways showed that this effect is independent of androgen receptor signaling. Instead, MECP2 appears to act by maintaining a constant c-myc level during antihormonal treatment. We further show that MECP2-expressing cells possess a functional p53 pathway and are still responsive to chemotherapeutic drugs.Oncogene advance online publication, 5 December 2005; doi:10.1038/sj.onc.1209179.
Lay Summary
A change in the amount of attached methyl groups on DNA is considered to be an early event in cancer development. As we know, MeCP2 is one of many proteins that binds to the methyl groups on DNA, and is involved in turning gene expression off and on. Thus, the role of MeCP2 and its related protein family members in the development of cancer - where gene expression is severely misregulated - has been an ongoing research area. In this study, the authors investigate the role of MeCP2 in controlling the growth of prostate cancer cells. They show that the lack of MeCP2 expression prevented the pancreatic cancer growth, whereas higher-than-normal amounts of MeCP2 stimulated the growth of cancer. In fact, this increase in MeCP2 expression level was sufficient by-itself to promote cancer growth, independent of the presence of any other cancer-causing factors. However, it should be noted that the MeCP2 mutations associated with Rett syndrome are not linked to an increased incidence of cancer.