Exogenous p27(Kip1) overexpression results in cell cycle regulation in the human prostate carcinoma cell lines tested, representing the first use of this vector on prostate cancer cell lines in vitro and in vivo.
Our laboratory has recently identified a 1 to 2 Mb homozygous deletion at 12p12-13 in a prostate cancer specimen and determined that the p27/kip1 gene lies within the deletion.
Together, these data implicate increased AKT activity in prostate tumor progression and androgen independence and suggest that diminished p27(Kip1) expression, which has been repeatedly associated with prostate cancer progression, may be a consequence of increased AKT activity.
These findings show a unique mechanism of cell growth inhibition by integrins and point to beta1C as an upstream regulator of p27(kip1) expression and, therefore, a potential target for tumor suppression in prostate cancer.
Prospective studies are urgently needed to confirm the independent prognostic value of decreased p27Kip1 protein expression together with overexpression of the p53 tumour suppressor protein in patients with localized prostate cancer.
However, the molecular-genetic analysis of a variety of human malignancies including prostate cancerfailed to identify any alteration at the p27Kip1 gene locus, therefore suggesting a loss of p27Kip1 protein expression to result from post-transcriptional/post-translational events or from so far unknown regulatory mechanisms.
Low p27Kip1 expression was an independent predictor of treatment failure on multivariate analysis of lymph node negative prostate cancers following radical retropubic prostatectomy (n = 102; P = 0.047).
This study was undertaken to identify and to assess potential alterations of p27KIP1 gene expression in patients with benign prostatic hyperplasia (BPH) and patients with prostate cancer.
The majority of primary prostate cancer specimens (68%) were totally negative for p27(Kip1) immunoreactivity, whereas the rest exhibited a significantly decreased p27(Kip1) expression, compared with the normal prostate (P < 0.01).