p27(Kip1) in prostate cancer, prognostic value and role in mediating effect of high-dose dihydrotestosterone in LNCaP

Abstract

p27 is a cyclin-dependent kinase inhibitor capable of inducing cell cycle arrest. p27 is abundant in multiple human epithelial tissues, however, the protein is less abundant and its expression more heterogeneous in malignancies from these tissues. In a study of archival tumours from patients with clinically localized adenocarcinoma, of the prostate, low p27 predicted shorter disease free survival. Androgen deprivation therapy prior to surgery tended to increase the p27 level. Low p27 in such turnouts was an even stronger predictor of early recurrence. G1 arrest of LNCaP cells by high dose dihydrotestosterone leads to a four-fold increase in p27 level, three-fold increase in p27 bound to cyclin E complexes. and inhibition of cyclin E-associated kinase activity. These data raise the hypothesis that changes in pathways that regulate p27 levels may contribute causally to tumour progression and growth modulation of human prostate cancer cells in response to various androgenic stimuli.