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A novel role for p12/CDK2AP1 cell cycle regulator in inhibiting cancer cell growth
Author(s) -
Zolochevska Olga,
Figueiredo Marxa L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.740.19
Subject(s) - bicalutamide , antiandrogens , prostate cancer , cell cycle , cancer research , cell cycle checkpoint , antiandrogen , cell growth , g1 phase , cyclin dependent kinase 2 , viability assay , apoptosis , growth inhibition , regulator , prostate , chemistry , biology , oncology , medicine , cancer , androgen receptor , biochemistry , gene
Prostate cancer is the second most prevalent type diagnosed in men in the western world, and since early‐stage cellular growth is dependent on androgens, androgen deprivation has been used as the main therapy intervention. However, following initial responsiveness, tumors relapse to an androgen‐independent state that ultimately leads to mortality, suggesting that alternatives are needed to enhance therapy efficacy. Since antiandrogens promote cell cycle arrest in part by decreasing CDK2 activity, we hypothesized that this effect could be enhanced by a novel CDK2‐associating molecule, p12/CDK2AP1. We assessed the effects of antiandrogen bicalutamide (cdx), p12, or both on cell cycle; both cdx and p12 induced cell cycle arrests, with a G1 arrest predominant for cdx‐treated, and either G1 or S‐G2 arrests for p12‐expressing cells. Interestingly, combination of cdx/p12 greatly augments the G1 arrest. Apoptosis was most prevalent with cdx/p12 and in the Lapc4 line. CCK8 assay revealed that the cdx/p12 combination was the most effective in reducing viability (up to 60%), colony formation ability, and cellular invasion (by up to 73%). Finally, although the effects of cdx or p12 varied among androgen‐dependent and ‐independent cell lines, the cdx/p12 combination was effective in reducing growth in all lines examined, representing a promising and novel combination for prostate cancer treatment.