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POLYISOPRENYLATED METHYLATED PROTEIN METHYL ESTERASE AS A PUTATIVE BIOMARKER AND DRUG TARGET FOR PROSTATE CANCER
Author(s) -
POKU ROSEMARY ANIWAA,
AMISSAH FELIX,
DUVERNA RANDOLPH,
AGUILAR BYRON J.,
LAMANGO NAZARIUS S.
Publication year - 2013
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.27.1_supplement.560.3
Subject(s) - lncap , prostate cancer , cancer research , cancer , prostate , metastasis , cancer cell , chemistry , androgen receptor , biology , medicine
Prostate cancer is the most frequently diagnosed cancer among men in the U.S., with an estimated 241,740 new cases and 28,170 deaths in 2012. Mutation and overexpression‐induced abnormal activities of polyisoprenylated proteins have been implicated in various neoplasms including prostate cancer. We determined whether polyisoprenylated methylated protein methyl esterase (PMPMEase) is overexpressed and hyperactive in prostate cancer, possibly contributing to progression and metastasis. PMPMEase specific activities were 4‐and 6‐fold higher in androgen‐dependent (22Rv1 and LNCaP) cells, 2‐ and 17‐fold higher in androgen‐independent (PC‐ 3 and DU 145) cells respectively, compared to normal WPE1‐NA22 prostate cells. Treatment of the cells with L‐28, a specific PMPMEase inhibitor induced apoptosis (EC50 of 1.8 to 4.6 μM). PMPMEase activity of the different cell lines followed a similar profile (IC50 of 2.3 to 130 μM). Analysis of prostate cancer tissue microarray for PMPMEase expression revealed intermediate, strong and very strong staining in 94.5% of the 92 adenocarcinoma cases compared to only trace staining in the normal tissue controls. The results suggest that PMPMEase is overexpressed, is hyperactive and is involved in prostate cancer cell progression. Its activity, immunoreactivity and inhibition could serve in the diagnosis and targeted therapeutic management of the disease.