Abstract
BACKGROUND. Macrophage inhibitory cytokine-1 (MIC-1) is a member of transforming growth factor-beta/bone morphogenetic protein (BMP) superfamily. Despite its potential role in prostatic regulation, little is known about its biological activity. METHODS. Expression profiling using 42K Affymetrix HuGeneFL® array was conducted to compare symptomatic benign prostatatic hyperplasia (BPH), histological BPH without symptoms, and normal prostate samples from donors. MIC-1 gene expression was analyzed by RT-PCR in pure culture of prostate epithelial and stromal cells, and prostate cancer cells, LNCaP, PC-3, DU-145. Influence of androgens on MIC-1 expression in LNCaP cells was analyzed by Northern blot. Enhancement of promoter activity of MIC-1 by androgens was examined using reporter assays. RESULTS. In contrast to normal prostates, MIC-1 gene was down-regulated in BPH samples with symptoms and histological BPH obtained from cystoprostatectomy specimens (P < 0.005 and P < 0.01, respectively). Expression level of MIC-1 in androgen-sensitive LNCaP cells was high and enhanced by androgens, whereas in the androgen-insensitive PC-3 and DU-145 cells the expression level was low. An 11 kb promoter region of MIC-1 gene was identified to be 6- to 12-fold activated by androgens. CONCLUSIONS. Down-regulation of MIC-1 may play a role in the development of BPH. MIC-1 is positively regulated by androgens, but other regulatory factors remain unclear.
Original language | English (US) |
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Pages (from-to) | 351-356 |
Number of pages | 6 |
Journal | Prostate |
Volume | 59 |
Issue number | 4 |
DOIs | |
State | Published - Jun 1 2004 |
Externally published | Yes |
Keywords
- Androgen regulation
- BPH
- MIC-1
- Prostate cancer
ASJC Scopus subject areas
- Oncology
- Urology