Abstract

PARP10 is an intracellular mono-ADP ribosyltransferase and recent reports suggest that it regulates proliferation of some cell types. However, its effect on the proliferation of colorectal carcinoma cells has not yet been systematically reported. We explored the influence of PARP10 on the proliferation of several colorectal carcinoma cell types and carried out initial studies on the underlying mechanisms. Inhibition of the enzymatic activity of PARP10 led to significantly decreases in proliferative ability in LoVo cells and CT26 cells in vitro and suppressed growth of CT26 tumours in the subaxilliary region in Balb/c mice in vivo. Cell-cycle arrest accompanied these observations. Expression of the nuclear transfer factor β-catenin and it translocation to the nucleus were also affected and the expression of its associated signal proteins Axin2 and c-Myb were increased and decreased, respectively. We demonstrate that PARP10 promotes proliferation of those colorectal carcinoma cells which express significant levels of PARP10. This promotion is suppressed when the enzymatic activity is inhibited. β-Catenin is likely to be the mediator of the antiproliferative effect.

中文翻译：

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PARP10影响结直肠癌细胞的增殖，一项初步研究

摘要

PARP10是一种细胞内单ADP核糖基转移酶，最近的报道表明它可以调节某些细胞类型的增殖。但是，其对结直肠癌细胞增殖的作用尚未系统报道。我们探索了PARP10对几种结直肠癌细胞类型增殖的影响，并对潜在的机制进行了初步研究。抑制PARP10的酶促活性会导致LoVo细胞和CT26细胞体外增殖能力显着降低，并抑制Balb / c小鼠体内腋下近端区CT26肿瘤的生长。这些观察伴随着细胞周期停滞。核转移因子β-catenin的表达及其易位至细胞核也受到影响，其相关信号蛋白Axin2和c-Myb的表达分别增加和减少。我们证明，PARP10促进表达大水平PARP10的那些结直肠癌细胞的增殖。当抑制酶活性时，这种促进作用被抑制。β-连环蛋白可能是抗增殖作用的介质。