| Choi KC, Tai CJ, Tzeng CR, Auersperg N, Leung PC |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=68 ------>confirm_bywho=tlc ------>insert_bywho=chenjtai ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author= ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=315 ------>medlineContent= ------>unit=E0111 ------>insert_date=20030521 ------>iam=2 ------>update_date= ------>author=??? ------>change_event=5 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=Biology of Reproduction ------>paper_name=Adenosine triphosphate activates mitogen-activated protein kinase in pre-neoplastic and neoplastic ovarian surface epithelial cells. ------>confirm_date=20031012 ------>tch_id=090048 ------>pmid=12493727 ------>page1=309 ------>fullAbstract=To investigate the role of ATP in ovarian tumorigenesis, the present study examined the expression of the P2U purinoceptor (P2U-R) and effect of ATP on growth stimulation in pre-neoplastic and neoplastic ovarian surface epithelial (OSE) cells. The immortalized OSE (IOSE) cell lines, including IOSE-29 (pre-neoplastic), IOSE-29EC (neoplastic), and OVCAR-3 (ovarian adenocarcinoma cell line) were used. Our results indicated that P2U-R mRNA was expressed and that ATP exerted a growth-stimulatory effect in IOSE-29, IOSE-29EC, and OVCAR-3. To investigate the mechanism of the growth-stimulatory effect, the activation of mitogen-activated protein kinases (MAPKs) by ATP was examined. Treatment with ATP resulted in MAPK activation in IOSE-29 and IOSE-29EC cells, whereas the stimulatory effect of ATP in cellular proliferation and MAPK activation was completely abolished in the presence of PD98059 (an MAPK/ERK kinase inhibitor) and staurosporin (a protein kinase C inhibitor), suggesting that the growth stimulatory effect of ATP is mediated via protein kinase C-dependent MAPK activation in pre-neoplastic and neoplastic OSE cells. In a time-dependent study, ATP significantly increased MAPK activity at 5-20 min in IOSE-29 cells. Activated MAPK declined to control levels after 20 min in these cells. Treatment with ATP significantly induced MAPK activation after 5 min and was sustained for 60 min in IOSE-29EC cells. In addition, treatment with ATP resulted in substantial phosphorylation of Elk-1, the Ets family transcriptional factor, confirming that ATP action is mediated by activation of MAPK. In conclusion, we have demonstrated that P2U-R was expressed and that ATP induced growth stimulation in IOSE and OVCAR-3 cells. Furthermore, treatment with ATP resulted in the activation of an MAPK cascade and phosphorylation of Elk-1 in IOSE-29 and IOSE-29EC cells. These results suggest that the MAPK cascade may be involved in growth stimulation in response to ATP in pre-neoplastic and neoplastic OSE cells. ------>tmu_sno=None ------>sno=7324 ------>authors2=None ------>authors3=None ------>authors4=None ------>authors5=None ------>authors6=None ------>authors6_c=None ------>authors=Choi KC, Tai CJ, Tzeng CR, Auersperg N, Leung PC ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Adenosine triphosphate activates mitogen-activated protein kinase in pre-neoplastic and neoplastic ovarian surface epithelial cells. ------>language=2 ------>check_flag= ------>submit_date= ------>country=None ------>no=1 ------>patent_SDate=None ------>update_bywho= ------>publish_year=2003 ------>submit_flag= ------>publish_month=None |