Meyer-Siegler K
Department of Urology, Bay Pines VA Medical Center, Bay Pines, FL 33744, USA.
J Interferon Cytokine Res. 2000 Sep;20(9):769-78. doi: 10.1089/10799900050151030.
Macrophage migration inhibitory factor (MIF) has been localized to the glandular epithelium of the prostate and stimulates the in vitro growth of prostate epithelial cells. [35S]Methionine labeling of MIF protein was used to determine if prostate cells synthesize and secrete this cytokine. The results demonstrated that the DU-145 prostate cancer cells secrete about twice the amount of a more stable protein compared with normal prostate epithelial cells. To investigate if differences in MIF mRNA levels account for the differences in MIF protein secreted by these cells, mRNA stability was analyzed by [3H]uridine incorporation. Following a 12-h pulse, DU-145 cells were found to contain four times the amount of [3H]uridine-labeled MIF mRNA, and this message exhibited a longer half-life than the message found in normal cells (33 h and 19 h, respectively). Nuclear run-on experiments confirmed that the MIF gene is transcribed at a greater rate (1.8-fold) in the DU-145 prostate cancer cells. This study documents, for the first time, that human prostate epithelial cells synthesize and secrete this cytokine. These results indicate that the increased levels of MIF found in prostate cancer cells is likely due to the increased protein and mRNA stability as exhibited by DU-145 cells.
巨噬细胞移动抑制因子（MIF）已定位到前列腺的腺上皮，并能刺激前列腺上皮细胞的体外生长。利用[35S]甲硫氨酸标记MIF蛋白来确定前列腺细胞是否合成并分泌这种细胞因子。结果表明，与正常前列腺上皮细胞相比，DU-145前列腺癌细胞分泌的一种更稳定的蛋白量约为其两倍。为了研究MIF mRNA水平的差异是否解释了这些细胞分泌的MIF蛋白的差异，通过[3H]尿苷掺入分析mRNA稳定性。经过12小时的脉冲处理后，发现DU-145细胞中[3H]尿苷标记的MIF mRNA量是正常细胞中的四倍，并且这条信息的半衰期比正常细胞中的信息更长（分别为33小时和19小时）。细胞核连续转录实验证实，MIF基因在DU-145前列腺癌细胞中的转录速率更高（1.8倍）。这项研究首次证明，人前列腺上皮细胞合成并分泌这种细胞因子。这些结果表明，前列腺癌细胞中MIF水平的升高可能是由于DU-145细胞所表现出的蛋白和mRNA稳定性增加。
