The role of microtubule regulatory protein Nur77 in metastasis of prostate cancer and its mechanism / 肿瘤

ABSTRACT

Objective: To investigate the clinical significance of Nur77 expression in prostate cancer tissues, and to explore the mechanism of its effect on the metastasis of prostate cancer. Methods: The expression of Nur77 in 72 cases of prostate cancer and 24 cases of benign prostatic hyperplasia was detected by immunohistochemistry. The relationship between Nur77 expression and the clinicopathological features of prostate cancer was analyzed. The co-localization of Nur77 and P-tubulin in prostate cancer PC-3 cells was detected by immunofluorescence. The interaction between Nur77 and β-tubulin was verified by co-immunoprecipitation assay. PC-3 cells were transfected with the different plasmids including pcDNA3.1-Nur77, Nur77ΔDBD, Nur77ΔTUBD and Nur77-shRNA by liposome, respectively. The soluble and polymerized tubulin fractions were differentially extracted and detected by Western blotting. The migration ability of PC-3 cells was detected by Transwell chamber assay. Results: The expression of Nur77 protein in prostate cancer tissues was higher than that in the benign prostatic hyperplasia tissues (P < 0.01). The expression level of Nur77 was downregulated with the ascending of N staging, M staging and Gleason score in prostate cancer (all P < 0.05). The Nur77 and β-tubulin were co-located and interacted with each other in the cytoplasm of PC-3 cells. Compared with the blank control group, the ratio of polymerized/soluble (P/S) tubulin was significantly increased in pcDNA3.1-Nur77 and Nur77ΔDBD groups, while the count of migratory cells was significantly decreased in pcDNA3.1-Nur77 and Nur77 ΔDBD group (all P < 0.05). In contrast, P/S ratio was significantly decreased, and the count of migratory cells was significantly increased in Nur77-shRNA group (both P < 0.05). Conclusion: Nur77 can inhibit the migration of PC-3 cells, which may be related to promoting tubulin polymerization into microtubule.