Analysis Of SP1/3 Expression Level And Regulation Function Of PP2A- Aa In Prostate Cancer DU145 And LNCaP

Protein phosphatases-2A(PP-2A) is a major serine/threonine phosphatase and accounts for more than 50% serine/threonine phosphatase activity in eukaryotes. The 36 k Da catalytic subunit(PP2Ac) interacts with the 65 k Da scaffold subunit making up the core enzyme, which is associated with a wide variety of B regulatory subunits to form a large number of heterotrimeric PP2 A holoenzymes.The complex of PP2 A holoenzyme structure laid a solid foundation for its function.PP2 A plays a very important role in the cell from cell cycle regulation, cell proliferation and death, individual organism development,dynamic balance of the cytoskeleton, cell migration to control of many signaling pathways.Current,much evidence proved that PP2 A is an important function factor.So far, study on the role of PP2 A in prostate cancer research has been focused on the catalytic and regulating for subunits. In contrast, little informtion is available about the function of the struction subunits of PP2 A in prostate cancer.In view of the situation, our laboratory conducted comparative study on the role of PP2 A in prostate cancer.We first explored how PP2A-Aa is regulates in prostate cancer cells LNCa P and DU145.Our results show that expression of PP2A-Aa in DU145 dropped significantly compaired with that in LNCa P. In addition, our laboratory studies have demonstrated that CREB is one of the important transcriptionfactors regulating PP2A-Aa. Convintent with a low level of PP2A-Aaexpression in DU145, CREB expression in this cell line is who significantly down-regulated. Our previous studies have also shown that other transcription factors, such as Sp1 and Sp3 in human lens epithelial cells and retinal pigment cells are involved in the regulation of PP2A-Aa,whether these transcription factors in prostate cancer cells LNCa P and DU145 have similar functions on PP2A-Aa expression remains to be investigated.In my work,I have demonstrated the followings: 1) by comparing the protein expression levels of PP2A-Aa with Sp1 and Sp3 in prostate cancer cells LNCa P and DU145, it is speculate that Sp3 may give positive regulation on PP2A-Aa.In contrast, Sp1 seems to negatively regulate PP2A-Aa.2) EMSA reveals that Sp1 / Sp3 could bind to PP2A-Aa gene promoter on in vitro;3) through overexpression of Sp1 and silence of Sp3 in LNCa P cells, I found that the expression of PP2A-Aawas down-regulated in responding to Sp1 overexpression and Sp3 silence in this cell line.4) through overexpression of Sp3 and silence of Sp1 in DU145 cells. It was found that PP2A-Aa was up-regulated in responding to Sp3 overexpression and Sp1 silence in this cell line.Together,my research results show that the Sp1 and Sp3 in prostate cancer cells LNCa P and DU145 are involved in regulation of the expression of PP2A-Aa.While Sp1 negatively regulates PP2A-Aa,Sp3positively regulates PP2A-Aaexpression in prostate cancer cells LNCa P and DU145 of Aa.These results help us to further understand shed some light to the control mechanism of PP2A-Aain prostate cancer cells,and anti-cancer mechanism of PP2A-Aaand also provide new information for the treatment of prostate cancer.