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 (PDT), 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. (C) 2003 Elsevier Science (USA). All rights reserved.