Inflammation-associated regulation of the macrophage inhibitory cytokine (MIC-1) gene in prostate cancer

Abstract

Macrophage inhibitory cytokine-1 (MIC-1), also known as prostate-derived factor (PDF), is a molecule of the TGF-β superfamily and has been associated with the progression of various types of diseases including prostate cancer. Initially identified from activated macrophages, the MIC-1 gene may provide a potential link between inflammation and prostate cancer. In this context, we performed MIC-1 expression analysis using mouse prostate tissues to determine whether there was any correlation with age and inflammation. Reverse transcription PCR analysis on RNA samples isolated from prostate lobes from prostate-specific antigen transgenic mice of varying ages revealed that MIC-1 gene expression is extremely low to non-detectable in the prostate tissues obtained from young mice, while its expression increases in the prostate tissues harvested from elderly mice. Increased MIC-1 gene expression in the mouse prostate was found to be associated with an increased level of infiltrating lymphocytes. To confirm this observation, we showed that inflammation-associated cytokines (IL-1β and TNF-α) significantly upregulate the secretion of the MIC-1 protein in a human prostate cancer cell line (LNCaP cells), while cytokines IL-6 and granulocyte macrophage colony-stimulating factor were less effective. Taken together, these data indicated that inflammation-associated cytokines may play a critical role in the functional regulation of the MIC-1 gene in the early stages of prostate cancer development. More studies are required to understand the biological activity of MIC-1 gene regulation in the development and progression of prostate cancer.