Nkx3.1 is a putative prostate tumor suppressor that is expressed exclusively in the prostate under the regulation of androgen, and p27(KIP1) functions as a cell proliferation inhibitor and apoptosis trigger by disrupting the cyclin-dependent kinase (CDK)-cyclin complex.
Down-regulation of p27(Kip 1) cyclin-dependent kinase inhibitor in prostate cancer: distinct expression in various prostate cells associating with tumor stage and grades.
The progression of LNCaP human prostate cancer cells to androgen independence involves decreased FOXO3a expression and reduced p27KIP1 promoter transactivation.
Elevated Skp2 protein expression in human prostate cancer: association with loss of the cyclin-dependent kinase inhibitor p27 and PTEN and with reduced recurrence-free survival.
The first describes mapping and cloning of a new candidate gene, ELAC2, whereas the second demonstrates how cooperation between Cdkn1b and Pten contribute to suppression of prostate tumors.
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 results indicate that frequent loss of the cyclin-dependent kinase inhibitor p27(Kip1) in human prostate cancer cells correlates with advancing histological aggressiveness, implicating deregulation of p27(Kip1) in prostate tumor progression.