Dysregulated expression of MIC-1/PDF in human prostate tumor cells.
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.
Karan
Dev
D
Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.
Chen
Siu-Ju
SJ
Johansson
Sonny L
SL
Singh
Ajay P
AP
Paralkar
Vishwas M
VM
Lin
Ming-Fong
MF
Batra
Surinder K
SK
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019485:Bone Morphogenetic Proteins; D018929:Cell Culture Techniques; D016207:Cytokines / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D055436:Growth Differentiation Factor 15; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D019485:Bone Morphogenetic Proteins; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D008565:Membrane Proteins; D012333:RNA, Messenger