title: Conversion of prostate cancer from hormone independency to dependency due to AMACR inhibition: involvement of increased AR expression and decreased IGF1 expression.
abstract: Androgen-independent prostate cancer eventually develops metastasis, and radical treatment may not be possible for patients at this stage. In this study, we examined the gene-expression profiles of two prostate cancer cell lines, LNCaP (androgen-dependent) and C4-2 (androgen-independent), using cDNA-microarray hybridization. We focused on the expression of alpha-methylacyl-CoA racemase (AMACR), whose expression is much higher in C4-2 than in LNCaP, and investigated its biological role in acquisition of androgen-independent cancer growth. Immunohistochemistry and Western blot analysis of subcellular fractions revealed that AMACR expression was much stronger in C4-2 than in LNCaP. Inhibition of AMACR expression using AMACR-siRNA induced an increase in the expression of androgen receptor (AR) and B-cell translocation gene 1, along with a decrease in the expression of genes associated with cancer progression, including insulin-like growth factor I and platelet-derived growth factor alpha, in C4-2 with compared to non-treated C4-2. BrdU analysis and MTT assay demonstrated that AMACR inhibition induced a significant decrease of cell viability in C4-2 when cultured in androgen-depleted serum, becoming consistent with that of LNCaP, suggesting that AMACR inhibition may induce an increase in the expression of AR and characteristic conversion of prostate cancer cells from hormone independency to hormone dependency. We suggest that AMACR inhibition may be a new strategy for treatment of patients with hormone-refractory prostate cancer.
authors: Department of Urology, Osaka Medical College, Takatsuki, Osaka 569-8686, Japan.
authors: Kiyoshi
authors: K
authors: Takahara
authors: Haruhito
authors: H
authors: Azuma
authors: Takeshi
authors: T
authors: Sakamoto
authors: Satoshi
authors: S
authors: Kiyama
authors: Teruo
authors: T
authors: Inamoto
authors: Naokazu
authors: N
authors: Ibuki
authors: Takeshi
authors: T
authors: Nishida
authors: Hayahito
authors: H
authors: Nomi
authors: Takanobu
authors: T
authors: Ubai
authors: Naoki
authors: N
authors: Segawa
authors: Yoji
authors: Y
authors: Katsuoka
mesh_terms: D015153:Blotting, Western; D045744:Cell Line, Tumor; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009376:Neoplasms, Hormone-Dependent / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000473:pathology*; D034741:RNA, Small Interfering; D019998:Racemases and Epimerases / Q000037:antagonists & inhibitors*; D011944:Receptors, Androgen / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D007334:Insulin-Like Growth Factor I; D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase