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Expression and functional analyses of PCA‐1 (ABH3) for molecular‐targeted therapy of prostate cancer
Author(s) -
Koike Kazuo,
Tsujikawa Kazutake,
Kitae Kaori,
Arima Hiroshi,
Suzuki Takashi,
Masai Seiko,
Fusamae Yasuyuki,
Konishi Noboru,
Yamamoto Hiroshi
Publication year - 2008
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.22.1_supplement.653.3
Subject(s) - du145 , prostate cancer , carcinogenesis , cancer research , biology , cancer , small interfering rna , rna interference , rna , prostate , transfection , microbiology and biotechnology , gene , lncap , genetics
Prostate cancer is the most common malignancy in men and the second leading cause of cancer death in Western countries. Many studies found out a number of genetic changes in prostate tumorigenesis, but it is not sufficient to understand the molecular mechanism of prostate tumorigenesis. We have recently identified and cloned a new gene named prostate cancer antigen‐1 (PCA‐1), which shows higher expression of both mRNA and protein in prostate cancer than in normal prostate tissue. Database analysis indicated that PCA‐1 has high similarity to Escherichia coli AlkB, a DNA and RNA alkylation damage repair enzyme, and belongs to the ABH (AlkB homologue) family as ABH3. PCA‐1 localized in cytoplasm as well as nuclei in some specimens of prostate cancer and in transfected HeLa cells, supporting that PCA‐1 might repair alkylated DNA and RNA in mammalian cells. To investigate the function of PCA‐1, we used the RNA interference technique to specifically deplete PCA‐1 mRNA in the prostate cancer cell lines DU145 and PC3. Transfection with PCA‐1 siRNAs causeda dramatic reduction in PCA‐1 at both mRNA and protein levels (to less than 20% of the levelsseen in control siRNA transfectants for 48 h culture). Interestingly, down‐regulation of PCA‐1 by siRNAs markedly inhibited cell proliferation and induced cell death by apoptosis. These results suggest that PCA‐1 may be a new molecular‐target for the treatment of human prostate cancer.