Dysregulated expression of MIC-1/PDF in human prostate tumor cells

Biochem Biophys Res Commun. 2003 Jun 6;305(3):598-604. doi: 10.1016/s0006-291x(03)00823-4.


As a part of the study to identify genes associated with hormone-refractory stage of human prostate cancer, we have recently identified several genetic and epigenetic changes that seem to be associated with the progression of androgen-sensitive to androgen-independent prostate tumor cells. In the present study, we report a novel gene, macrophage inhibitory cytokine-1 (MIC-1) also known as prostate derived factor (PDF), that was highly expressed in androgen-independent LNCaP-C81 cells and its metastatic variant LNCaP-Ln3 compared to androgen-sensitive LNCaP-C33 cells. The MIC-1/PDF expression was dysregulated (very low to non-detectable) in the androgen-independent PC3 and DU145 cells. Interestingly, serum factors demonstrated a differential regulation of MIC-1/PDF in the androgen-sensitive and the androgen-independent cells of LNCaP cells. Immunohistochemical analysis on 15 prostatic adenocarcinomas showed a weak staining in the benign prostatic glandular area (intensity score 2.38+/-0.25; n=13), while the immunoreactivity was significantly stronger (p<0.05) in areas of adenocarcinoma (score 7.33+/-0.88; n=15). Altogether, these data suggest that the serum factors (including androgens and cytokines) might contribute to the regulation of the MIC-1/PDF gene that seems to be associated with the progression of prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Bone Morphogenetic Proteins
  • Cell Culture Techniques
  • Cytokines / analysis
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Growth Differentiation Factor 15
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • RNA, Messenger / biosynthesis
  • Tumor Cells, Cultured


  • Bone Morphogenetic Proteins
  • Cytokines
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Membrane Proteins
  • RNA, Messenger