Disruption of androgen receptor function inhibits proliferation of androgen-refractory prostate cancer cells.
Prostate cancer cells depend on androgens and the androgen receptor (AR) for survival. However, after androgen ablation therapy, tumors relapse to an androgen-refractory state. To determine whether the androgen receptor is critical for proliferation of androgen-refractory prostate cancer cells, we disrupted the activity of the androgen receptor with an antibody and an AR mRNA hammerhead ribozyme in the following cell lines: LNCaP (androgen-sensitive), LNCaP-Rf and LNCaP-C4 (androgen-refractory), and DU-145 (androgen-insensitive). Microinjection of either antibody or ribozyme inhibited proliferation of androgen-refractory cells. These findings demonstrate that the AR is critical for proliferation of androgen-refractory cells, even in the absence of androgens.
Zegarra-Moro
Ofelia L
OL
Department of Biochemistry, Mayo Clinic, Rochester, Minnesota 55905, USA.
Schmidt
Lucy J
LJ
Huang
Haojie
H
Tindall
Donald J
DJ
D000726:Androgen Antagonists / Q000494:pharmacology; D059002:Androgen Receptor Antagonists; D000912:Antibodies, Neoplasm / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000473:pathology; D011471:Prostatic Neoplasms / Q000473:pathology*; D016337:RNA, Catalytic / Q000494:pharmacology; D011944:Receptors, Androgen / Q000235:genetics / Q000276:immunology / Q000502:physiology
D000726:Androgen Antagonists; D059002:Androgen Receptor Antagonists; D000912:Antibodies, Neoplasm; D016337:RNA, Catalytic; D011944:Receptors, Androgen; C427204:hammerhead ribozyme