Expression And Significance Of Five Membrane Proteins Including Dysferlin In Prostate Cancer

Carcinoma of the prostate is one of the commonest forms of male malignant disease; the incidence of which increases with age, particularly beyond 50 years. Because of the complicated bionomics of prostatic carcinoma, which earlier period clinical symptoms is not significant, most patients have clinical symptoms and then go to the hospital are almost occupying advanced stage, and even part of which has already spreaded, early diagnosis of the prostatic carcinoma is to become more and more important reasearch topic in the urinary surgery territory.In this studies, we according to the achivements of the early series experiments, which from the analyse the difference expressions of the membrane proteins in the human nomal prostate cells, PC-3 and PC-3M cells by using the technique of two-dimensional difference gel electrophoresis(2D-DIGE) and to combine the Shotgun-MS technique. We havechosenDysferlin(230KD),PHEX(90KD),EDG2(43KD),KV1.1(57-59KD) and IL-3Rβ(130KD) five proteins from the membrane proteins of PC-3 and PC-3M cells, and to detect its expressions on PC-3, PC-3M cells and on human nomal prostate (cancer) tissue respectively, to aim at searching new proteins which have important significance in the development of the prostate cancer and diagnosis of the prostate cancer.Results:(1) RT-PCR analysis shows that Dysferlin mRNA and IL-3RβmRNA only express on PC-3 cells, its have no expression on the nomal prostate tissue(outer zone) and PC-3M cells; PHEXmRNA express both on PC-3 cells and on PC-3M cells, its have no expression on the nomal prostate tissue(outer zone); EDG2mRNA express on the nomal prostate tissue(outer zone), PC-3 cells and on t PC-3M cells; KV1.1 mRNA have no expression on the nomal prostate tissue(outer zone), PC-3 cells and PC-3M cells.(2) The result from immunocytochemstry indicated Dysferlin,PHEX and KV1.1 proteins is positive both in PC-3 cells and PC-3M cells, and is negative in the nomal prostate tissue(outer zone) epithelial cells; IL-3Rβprotein is positive in PC-3 cells, and is negative in the nomal prostate tissue(outer zone) and PC-3M cells; EDG2 protein is positive in the nomal prostate tissue(outer zone) epithelial cells, PC-3 cells and PC-3M cells.Dysferlin has a molecular mass of 237 kDa and its expression is highest in skeletal muscle, heart and kidney[1]. Dysferlin is located in the sarcolemma of muscle fibers and is absent in dysferlinopathies. At present, the research of the Dysferlin mainly to centralize in the myopathy, and have no literature reports on if its has expressed in tumor.(3) Therefore, we choose Dysferlin to continous study, the result from Western blot indicated Dysferlin is positive both in PC-3 cells and PC-3M cells, and is negative in the nomal prostate tissue(outer zone); to view its significance in the development of the prostate cancer, we have to detect its expression in different Gleason grades and in different pathology histological type prostate cancer tissue specimens by using the immunohistochemistry, the results indicates : Dysferlin protein is negative in the nomal prostate tissue(outer zone) epithelial cells, and is positive in the prostate tissues, the positive rates of Dysferlin in 35 prostate carcinoma tissues were 91.4%; which expression have reduced following the raise of the prostate cancer's Gleason grade. There are significant differece of expressions of Dysferlin among different Gleason grading(P﹤0.05).In addtion, the levels of Dysferlin in adenocarcinoma of prostate significantly higher levers in the duct carcinoma of prostate and in the transitional cell carcinoma of the prostate(P﹤0.05). Dysferlin's higher expression in the adenocarcinoma of prostate to cue that its expression has some correlations with pathology histological type. The positive rate of Dysferlin's expression in all the metastasis of the prostate cancer is 100.0%.Above results show that Dysferlin may play an important role in the progress of prostate cancer, and its probably to participate to the process of the prostate metastasis, and to establish experiment foundation of Dysferlin'fuction in the metastasis of the prostate cancer, it can provide new target for diagnosis of prostate carcinoma metastasis.