Expression Of A Disintegrin And Metalloprotease 22 And Its Role In Prostate Cancer

Prostate cancer is the second ranked carcinoma in developed countries an is the third mortal disease among the male. The morbidity of prostate cancer is obviously lower than the developed countries but with the increased tendency because of increased life span, westernized diet and improvement of diagnosis technology and it ranked the third in male urine malignancy. The etiology of prostate cancers was not clear. The microenvironments of tumor should be vital. A disintegrin and metalloproteinases, abbreviated as ADAMs were nearly identified and with vital function. This study was aimed to explore ADAM22, one member of the family distribution and role in prostate carcinomas.Aim: To explore the distribution and function of ADAM22 in prostate cancers. To prepare its specific monoclonal antibodies. To discuss the modification of cytokines targeting ADAM22 and find its role in potential roles during tumor apoptosis. All these will help us to understand etiology and pathology of prostate cancer, which will supply new evidences for therapy and prognosis for prostate cancers. Methods: ADAM22 cDNA was cloned with RT-PCR and its extracellular domain subcloned and inserted into plasmid. The recombinant protein was induced and purified. Mice were immunized with the recombinant protein and the corresponding monoclonal antibodies were prepared and characterized by flow cytometry, western blot and immunohistochemistry. Transcription and expression of ADAM22 induced by TNF-αwere identified by real-time RT-PCR and flow cytomety and its involved signaling were tested by specific inhibitors. Cleavage of Fas by ADAM22 and the potential role of resistance to apoptosis were identified.Results: ADAM22 cDNA was cloned successfully and its recombinant proteins were expressed. Three strains of mAb specific for ADAM22 were prepared. One of them was applicable in flow cytometry and the other was usable in IHC. ADAM22 was positive in prostate cancer tissues and most of it was located in gland-like and interstitial cells. TNF-αincreased transcription and expression of ADAM22 by activation of p38MAPK and NF-κB。ADAM22 sheded Fas and induced apoptosis resistance, which was blocked by the mAb we prepared previously.Conclusion: 1. ADAM22 was positive in prostate cancer tissues and cells. 2. TNF-αincrease ADAM22 expression. 3. ADAM22 induced apoptosis resistance of tumor cells by shedding of Fas.