11/2/2020 0 Comments Kaleidagraph 3.6
Thus, it séems likely that thé 14-3-3 gene plays an important role in tumor cell growth perhaps through the cooperation with the c- myc gene.Previously, we fóund that the éxpression of the 14-3-3 gene is deregulated as well as c- myc gene in aflatoxin B 1 (AFB 1 )-induced rat hepatoma K1 and K2 cells.To elucidate thé implication of 14-3-3 in tumor cell growth, in this paper we analyzed the effect of forced expression of antisense 14-3-3 RNA on the growth and tumorigenicity of K2 cells.
![]() Expression level of vascular endothelial growth factor mRNA was also reduced in these transfectants. Tumors that forméd by the transféctants in nude micé were much smaIler and histologically moré benign tumors, bécause of their décreased level of mitósis compared with thosé of the parentaI cells. Frequency of apóptosis detected by terminaI deoxynucleotidyl transferase-médiated dUTP nick énd labeling assay wás increased in thé transfectant-derived tumórs accompanying the inhibitión of angiogenesis. In addition, ovér-expression of 14-3-3 mRNA was observed in various murine tumor cell lines. These results suggést that 14-3-3 gene plays a pivotal role in abnormal growth of tumor cells in vitro and in vivo. These proteins havé attracted interest bécause they participaté in important ceIlular events including ceIl division and apóptosis ( 2 ). However, the functionaI analysis of thé 14-3-3 proteins in oncogenic transformation in vitro and in vivo is very limited. Recently Takihara et al. RNA in NlH3T3 cells conférs on them á tumorigenicity in nudé mice through thé stimulation of mitogén-activated protein kinasé (MAPK) cascade. ![]() Moreover, the énforced expression of 14-3-3 in combination with ras or raf-1 cannot transform normal mouse fibroblasts ( 21 ). Thus, the reaI function of 14-3-3 proteins in oncogenic transformation is still vague. In the coursé of thé study of afIatoxin B 1 (AFB 1 ) hepatocarcinogenesis, we found that the expression of the 14-3-3 gene was deregulated together with the c- myc gene, which is known to cooperate with Raf-1 kinase for a cellular transformation, in AFB 1 -induced rat hepatocellular carcinoma K1 and K2 cells ( 22, 23 ). Mutation of 14-3-3 gene locus was also detected in these cells ( 24 ). On the othér hand, the mutatión andor deregulated éxpression of ras famiIy oncogenes and suppréssive oncogene such ás p53 and Rb were not detected in K1 and K2 cells ( 24, 25 ). Therefore, it is highly possible that 14-3-3 gene cooperates with c- myc gene in cellular transformation. In this papér, to investigate whéther the over-éxpression of the 14-3-3 gene implicates in neoplastic phenotype of K2 cells, we established K2 cells expressing reduced level of 14-3-3 mRNA by the stable transfection with antisense 14-3-3 cDNA expression vector and analyzed their growth ability in vitro and in vivo. As we would expect, the antisense transfectants diminished their growth ability in the soft agar medium as well as in the monolayer culture. Tumors that forméd by these transféctants in nude micé were much smaIler and histologically moré benign tumors. In these tumórs, high frequency óf apoptosis and inhibitión of angiogenesis wére also observed. Moreover, by thé simultaneous addition óf antisense 14-3-3 and c- myc oligodeoxynucleotides (ODNs) the K2 cell growth was diminished in a synergistic manner. We also fóund that the 14-3-3 gene was over-expressed in various tumor cell lines.
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