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

Dubey,Seema; VanVeldhuizen,Peter; Holzbeierlein,Jeffrey; Tawfik,Ossama; Thrasher,J.   Brantley; Karan,Dev

doi:10.3892/ol.2012.635

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

Authors:
- Seema Dubey
- Peter VanVeldhuizen
- Jeffrey Holzbeierlein
- Ossama Tawfik
- J. Brantley Thrasher
- Dev Karan
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Affiliations: Department of Urology, University of Kansas Medical Center, Kansas City, KS 66160, USA, Cancer Research Unit, Veterans Affairs Medical Center, Kansas City, MO 64128, USA, Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA
Published online on: March 6, 2012 https://doi.org/10.3892/ol.2012.635
Pages: 1166-1170

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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.

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