Tseng, Ya-Shih., |
------>authors3_c=None ------>paper_class1=1 ------>Impact_Factor=None ------>paper_class3=2 ------>paper_class2=1 ------>vol=288 ------>confirm_bywho=None ------>insert_bywho=uro ------>Jurnal_Rank=None ------>authors4_c=None ------>comm_author=1 ------>patent_EDate=None ------>authors5_c=None ------>publish_day=None ------>paper_class2Letter=None ------>page2=414 ------>medlineContent= ------>unit=E0117 ------>insert_date=20040521 ------>iam=3 ------>update_date=None ------>author=??? ------>change_event=1 ------>ISSN=None ------>authors_c=None ------>score=500 ------>journal_name=Experimental Cell Research ------>paper_name=Ha-ras overexpression mediated cell apoptosis in the presence of 5 fluorouracil ------>confirm_date=None ------>tch_id=092056 ------>pmid=12915131 ------>page1=403 ------>fullAbstract=By using a mouse NIH3T3 derivate designed 7-4 harboring the inducible Ha-ras oncogene, we demonstrated the close relationship between Ha-ras expression level and sensitization of 5-flurouracil (5-FU)-treated cells. Further studies revealed that the cells susceptible to 5-FU treatment died of apoptosis, which was demonstrated by caspase-3 activation, loss of mitochondria membrane potential (MMP), and DNA fragmentation. The 7-4 cells coexpressing dominant negative Ras (Ras(Asn17)), dominant negative Raf-1 (Raf-1(CB4)), Bcl-2, or active form of phosphatidylinositol 3-kinase (PI3K) became resistant to 5-FU, and apoptosis was prevented. In contrast, the cells coexpressing dominant negative Rac 1 (Rac1(Asn17)) or dominant negative Rho A (RhoA(Asn19)) showed no change of sensitivity to 5-FU. These results indicate that Ras, Bcl-2, as well as Raf-1 and PI3K pathways play pivotal roles in 5-FU-induced apoptosis under Ha-ras-overexpressed condition. Aberrant levels of cyclin E and p21(Cip/WAF-1) expression as well as Cdc 2 phosphorylation at Tyrosine 15 suggest that perturbation of G1/S and G2/M transitions in cell cycle might be responsible for 5-FU triggered apoptosis. Sensitization of Ha-ras-related cells to 5-FU was also demonstrated in human bladder cancer cells. Through understanding the mechanism of 5-FU induced apoptosis in tumor cells, a new direction toward the treatment of Ha-ras oncogene-related cancers with 5-FU at more optimal dosages is possible and combinational therapy with other drugs that suppress PI3K and Bcl-2 activities can also be considered. ------>tmu_sno=None ------>sno=9426 ------>authors2=Tseng, Ching-Cherng. ------>authors3=Chiu, Allen. W., ------>authors4= ------>authors5= ------>authors6= ------>authors6_c=None ------>authors=Tseng, Ya-Shih., ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c=None ------>publish_area=None ------>updateTitle=Ha-ras overexpression mediated cell apoptosis in the presence of 5-fluorouracil. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2003 ------>submit_flag=None ------>publish_month=None |