MODULATION OF MDR-1 GENE BY MIF AND GSTpi WITH DRUG RESISTANCE GENERATION IN HORMONE INDEPENDENT PROSTATE CANCER

Abstract

& The expression of MIF and GSTpi were upregulated in prostate cancer cells with mulitdrug resistant phenotype. The aim of this study is to determine the relationship between these genes and multidrug resistance (mdr-1) gene in acquired multidrug resistance of prostate cancer. The expression of MIF, GSTpi and gp-170 in multidrug resistant (MDR) subline or native cells were determined using flow cytometry and western blotting. The mRNA level of various genes was analyzed with RT-PCR method. The chemosensitivity of tumor cells and stable transfectants to paclitaxel was measured using MTT (tetrazolium bromide) assay. The protein levels of MIF, GSTpi and gp-170 increased in MDR sublines of prostate cancer when compared with their parental cells. The MIF and GSTpi stable transfectants expressed higher MIF and GSTpi protein levels than their parental cells in western blotting analysis, respectively. The expression of mdr-1 gene and the production of pg-170 were also increased in either MIF or GSTpi stable transfectants when compared with vector control by using RT-PCR and flow cytometric analysis. The MTT results demonstrated that the increased chemoresistance was correlated with the increased production of gp-170 protein in either MIF or GSTpi transfectants. The upregulation of MIF and GSTpi during the development of acquired drug resistance of hormone independent prostate cancer may simultaneously and partially modulate the activation of gp-170.

Elevated expression of macrophage migration inhibitory factor correlates with tumor recurrence and poor prognosis of patients with gliomas

“…Recent studies have also demonstrated that MIF modulates the biological response in different cell types by inducing the nuclear factor-kappa B (NF-jB), Erk1/2 and activating protein-1(AP-1) signaling pathways, or by binding the CD74/CD44 receptor complex [9]. In addition, MIF has been shown to be involved in chemoresistance and to influence the prognosis in various malignancies [10][11][12]. Various studies have suggested that MIF also promotes tumor-associated angiogenesis by stimulating angiogenic factors, and consequently induces poor prognosis [13,14].…”

Macrophage migration inhibitory factor contributes angiogenesis by up‐regulating IL‐8 and correlates with poor prognosis of patients with primary nasopharyngeal carcinoma

“…Recent studies demonstrated that MIF could directly promote cell survival through activation of the PI3K/Akt pathway in breast cancer and gastric cancer cells 13, 14. In addition, MIF has been shown to involve in the chemoresistance and influence the prognosis in various malignancies 15–17. Various studies have suggested that MIF also promotes tumor‐associated angiogenesis by stimulating angiogenic factors, and consequently induces poor prognosis 18, 19.…”

Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses

“…Increased expression of HuMIF has been reported in several cancers, including prostate cancer (16)(17)(18). Studies show high expressers of HuMIF have a heightened risk of prostate cancer, as well as a significant increase in prostate cancer progression and drug resistance (17)(18)(19)(20)(21)(22)(23). Several clinical studies have shown HuMIF production correlates with both tumor aggressiveness and metastatic potential (23,24).…”