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Human 14-3-3 gamma protein results in abnormal cell proliferation in the developing eye of Drosophila melanogaster

机译:人类14-3-3γ蛋白在果蝇的发育中导致细胞异常增殖

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Background 14-3-3 proteins are a family of adaptor proteins that participate in a wide variety of cellular processes. Recent evidence indicates that the expression levels of these proteins are elevated in some human tumors providing circumstantial evidence for their involvement in human cancers. However, the mechanism through which these proteins act in tumorigenesis is uncertain. Results To determine whether elevated levels of 14-3-3 proteins may perturb cell growth we overexpressed human 14-3-3 gamma (h14-3-3 gamma) in Drosophila larvae using the heat shock promoter or the GMR-Gal4 driver and then examined the effect that this had on cell proliferation in the eye imaginal discs of third instar larvae. We found that induction of h14-3-3 gamma resulted in the abnormal appearance of replicating cells in the differentiating proneural photoreceptor cells of eye imaginal discs where h14-3-3 gamma was driven by the heat shock promoter. Similarly, we found that driving h14-3-3 gamma expression specifically in developing eye discs with the GMR-Gal4 driver resulted in increased numbers of replicative cells following the morphogenetic furrow. Interestingly, we found that the effects of overexpressing h1433 gamma on eye development were increased in a genetic background where String (cdc25) function was compromised. Conclusion Taken together our results indicate that h14-3-3 gamma can promote abnormal cell proliferation and may act through Cdc25. This has important implications for 14-3-3 gamma as an oncogene as it suggests that elevated levels of 14-3-3 may confer a growth advantage to cells that overexpress it.
机译:背景14-3-3蛋白是衔接子蛋白家族,其参与多种细胞过程。最近的证据表明,这些蛋白质在某些人类肿瘤中的表达水平升高,为它们参与人类癌症提供了间接证据。但是,这些蛋白在肿瘤发生中的作用机理尚不清楚。结果为了确定14-3-3蛋白的升高水平是否会干扰细胞生长,我们使用热激启动子或GMR-Gal4驱动程序,然后在果蝇幼虫中过表达了人14-3-3γ(h14-3-3γ)。检验了这对三龄幼虫眼球中的细胞增殖的影响。我们发现,h14-3-3γ的诱导导致在热成像启动子驱动h14-3-3γ的眼球间盘的分化前体感光细胞中复制细胞的异常出现。同样,我们发现用GMR-Gal4驱动程序驱动h14-3-3γ的表达特别是在发育中的眼球中导致形态发生犁沟后复制细胞数量的增加。有趣的是,我们发现过表达h1433γ对眼睛发育的影响在String(cdc25)功能受损的遗传背景下有所增加。结论综上所述,我们发现h14-3-3γ可以促进细胞异常增殖,并可能通过Cdc25起作用。这对于14-3-3γ作为癌基因具有重要意义,因为它表明14-3-3的升高水平可能赋予过表达它的细胞以生长优势。

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