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

Yoshiyuki Kakehi, Takehiko Segawa, Xiu Xian Wu, Prakash Kulkarni, Rajiv Dhir, Robert H. Getzenberg

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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 languageEnglish (US)
Pages (from-to)351-356
Number of pages6
Issue number4
StatePublished - Jun 1 2004


  • Androgen regulation
  • BPH
  • MIC-1
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology


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