Format

Send to

Choose Destination
Prostate. 2004 Jun 1;59(4):351-6.

Down-regulation of macrophage inhibitory cytokine-1/prostate derived factor in benign prostatic hyperplasia.

Author information

1
Department of Urology, Faculty of Medicine, Kagawa University, Miki-cho, Kita-gun, Kagawa, Japan. kakehi@kms.ac.jp

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.

PMID:
15065082
DOI:
10.1002/pros.10365
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center