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首页> 外文期刊>Molecular cancer research: MCR >Suppression of cell proliferation and signaling transduction by connective tissue growth factor in non-small cell lung cancer cells.
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Suppression of cell proliferation and signaling transduction by connective tissue growth factor in non-small cell lung cancer cells.

机译:非小细胞肺癌细胞中结缔组织生长因子的细胞增殖抑制和信号转导。

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摘要

Connective tissue growth factor (CTGF) is a secreted protein that belongs to CCN family. The proteins in this family are implicated in various biological processes, such as angiogenesis, adhesion, migration, and apoptosis. In this study, we explored the roles of CTGF in lung tumorigenesis. The expression levels of CTGF in 58 lung cancer samples were reduced by >2 fold in 57% of the samples compared with matched normal samples using real-time reverse transcription-PCR. These results were confirmed by immunohistochemical staining for CTGF in normal lung epithelia and lung cancer. Cellular proliferation was inhibited in non-small cell lung cancer (NSCLC) cell lines NCI-H460, NCI-H520, NCI-H1299, and SK-MES-1 by CTGF overexpression. Partially purified CTGF suppressed lung cancer cell growth. The growth inhibition caused by CTGF overexpression was associated with growth arrest at G(0)-G(1) and prominent induction of p53 and ADP ribosylation factor. Most interestingly, overexpression of CTGF suppressed insulin-like growth factor-I-dependent Akt phosphorylation and epidermal growth factor-dependent extracellular signal-regulated kinase 1/2 phosphorylation. In summary, NSCLC cells expressed decreased levels of CTGF compared with normal lung cells; this lower expression has an effect on lung cancer cell proliferation and its cellular response to growth factors. Our data suggest that CTGF may behave as a secreted tumor suppressor protein in the normal lung, and its expression is suppressed in many NSCLCs.
机译:结缔组织生长因子(CTGF)是一种分泌蛋白,属于CCN家族。该家族中的蛋白质与各种生物学过程有关,例如血管生成,粘附,迁移和凋亡。在这项研究中,我们探讨了CTGF在肺肿瘤发生中的作用。使用实时逆转录PCR,与匹配的正常样品相比,在58个肺癌样品中,CTGF的表达水平在57%的样品中降低了> 2倍。正常肺上皮细胞和肺癌中CTGF的免疫组织化学染色证实了这些结果。非小细胞肺癌(NSCLC)细胞系NCI-H460,NCI-H520,NCI-H1299和SK-MES-1的细胞增殖受到CTGF过度表达的抑制。部分纯化的CTGF抑制了肺癌细胞的生长。 CTGF过表达引起的生长抑制与在G(0)-G(1)处的生长停滞以及p53和ADP核糖基化因子的显着诱导有关。最有趣的是,CTGF的过表达抑制了胰岛素样生长因子-I依赖的Akt磷酸化和表皮生长因子依赖的细胞外信号调节的激酶1/2磷酸化。总之,与正常肺细胞相比,NSCLC细胞表达的CTGF水平降低。这种较低的表达对肺癌细胞增殖及其对生长因子的细胞反应有影响。我们的数据表明,CTGF可能在正常肺中充当分泌的肿瘤抑制蛋白,并且在许多NSCLC中其表达均被抑制。

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