The Research About The Role Of Transcription Factor CREB In Regulating The Cell Cycle And Its Mechanism In Cervial Cancer

Backgrounds Cervical cancer is the most common cause of women’s cancer deaths aroundthe world, seriously threaten the women’s healthy. Many factors influence the development ofcancers because its tumorigenesis is a complex process. Gene expression was changed during theoncogenesis. In recent observations, people think highly of the function about the transcriptionfactor cyclic adenosine monophosphate responsive element binding protein (CREB) in theprogresses of tumorigenesis and development. Expression of target genes mediated by CREB wasobserved to play an important role in the progress. In our further researches, we found that Bcl2,was decreased in the process of TCS-induced cell apoptosis, especially, this process was mediatedby the transtription factor CREB. On the other hand, we reported that the proliferation of cervicalcarcinoma cells was inhibited after they were treated with TCS, furthermore, PKC/MAPK/CREBsignal pathway was involved. Therefore, these studies revealed that the expression of proteinCREB maybe correlated with the tumorigenesis and development of the cervical carcinoma.However, nothing is known about the inhibiton of cell proliferation, especially roles of CREBduring these process.In this study, we firstly designed to study the regulating mechanism of CREB in theproliferation of cervical carcinoma cells; secondly to exploit the roles of cyclins in this progress;thirdly by rebuilding the normal and mutitued plasmids of total genes of CREB, then tranfectedcells in order to provide an important evidence to reveal the function of CREB in the cell cycleregulation, which by the way of regulating the cell cyclins and further changed the moleculemechanism of the cell cycle.Methods (1) The best disposed time and concentration of TCS were determined by theanalysis of MTT.(2) Flow Cytometry (FACS) was used to analyse cell proliferation and cell cyclearrest.(3) The transfections for PCI neo/CREB1plasmid and negative control PCI neo/CREB1-Mplasmid into cervical carcinoma cells, the cells were performed using Lipofectamine2,000according to the manufacturer’s protocol.(4) To determine whether the expression of targetproteins changed after the handling, Western blot were applied.Results After the cervical carcinoma cells disposed to TCS,(1) cell cycle was arrested at G1phase,(2) The expression of p-CREB and cyclin D1/E were decreased when disposed by TCS, butthe protein CREB remainded the same level,(3) The expression of p-CREB and cyclin D1/E were down-regulated when transfected the PCI neo/CREB1-M plasmid and the low expression of p-CREB and cyclin D1/E was reversed when transfected the PCI neo/CREB1plasmid.Conclusions This study suggested that CREB down-regulated the expression of cyclin D1/E,then caused the cell ceyle arrest of G1.