The methyl-CpG-binding protein MECP2 is required for prostate cancer cell growth.
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.
Bernard
D
D
Molecular Virology Laboratory, Free University of Brussels, Brussels, Belgium. dbernard@ulb.ac.be
Gil
J
J
Dumont
P
P
Rizzo
S
S
Monté
D
D
Quatannens
B
B
Hudson
D
D
Visakorpi
T
T
Fuks
F
F
de Launoit
Y
Y
D000728:Androgens / Q000502:physiology; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D049109:Cell Proliferation; D002470:Cell Survival; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000502:physiology*; D011467:Prostate / Q000166:cytology; D011471:Prostatic Neoplasms / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D011944:Receptors, Androgen; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D000728:Androgens; D018931:Antineoplastic Agents, Hormonal; C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2; D016271:Proto-Oncogene Proteins c-myc; D011944:Receptors, Androgen