Paul O'Gorman Leukaemia Research Centre, University of Glasgow, Glasgow, UK.
BMC Cancer. 2010 Nov 30;10:657. doi: 10.1186/1471-2407-10-657.
Coiled-coil domain containing 115 (Ccdc115) or coiled coil protein-1 (ccp1) was previously identified as a downstream gene of fibroblast growth factor 2 (FGF2) highly expressed in embryonic and adult brain. However, its function has not been characterised to date. Here we hypothesized that ccp1 may be a downstream effecter of FGF2, promoting cell proliferation and protecting from apoptosis.
Forced ccp1 expression in mouse embryonic fibroblast (MEF) and neuroblastoma SK-N-SH cell line, as well as down-regulation of ccp1 expression by siRNA in NIH3T3, was used to characterize the role of ccp1.
Ccp1 over-expression increased cell proliferation, whereas down-regulation of ccp1 expression reduced it. Ccp1 was able to increase cell proliferation in the absence of serum. Furthermore, ccp1 reduced apoptosis upon withdrawal of serum in SK-N-SH. The mitogen-activated protein kinase (MAPK) or ERK Kinase (MEK) inhibitor, U0126, only partially inhibited the ccp1-dependent BrdU incorporation, indicating that other signaling pathway may be involved in ccp1-induced cell proliferation. Induction of Sprouty (SPRY) upon FGF2 treatment was accelerated in ccp1 over-expressing cells.
All together, the results showed that ccp1 regulates cell number by promoting proliferation and suppressing cell death. FGF2 was shown to enhance the effects of ccp1, however, it is likely that other mitogenic factors present in the serum can also enhance the effects. Whether these effects are mediated by FGF2 influencing the ccp1 function or by increasing the ccp1 expression level is still unclear. At least some of the proliferative regulation by ccp1 is mediated by MAPK, however other signaling pathways are likely to be involved.
卷曲螺旋结构域蛋白 115（Ccdc115）或卷曲螺旋蛋白 1（ccp1）先前被鉴定为成纤维细胞生长因子 2（FGF2）的下游基因，在胚胎和成人脑中高表达。然而，其功能至今尚未确定。在这里，我们假设 ccp1 可能是 FGF2 的下游效应物，促进细胞增殖并防止细胞凋亡。
在小鼠胚胎成纤维细胞（MEF）和神经母细胞瘤 SK-N-SH 细胞系中强制表达 ccp1，以及通过 siRNA 在 NIH3T3 中下调 ccp1 表达，用于研究 ccp1 的作用。
ccp1 的过表达增加了细胞增殖，而 ccp1 表达的下调则降低了细胞增殖。ccp1 能够在没有血清的情况下增加细胞增殖。此外，ccp1 减少了 SK-N-SH 中血清去除后的细胞凋亡。丝裂原激活的蛋白激酶（MAPK）或 ERK 激酶（MEK）抑制剂 U0126 仅部分抑制了 ccp1 依赖性 BrdU 掺入，表明其他信号通路可能参与了 ccp1 诱导的细胞增殖。在 FGF2 处理后，ccp1 过表达细胞中 Sprouty（SPRY）的诱导加速。
总之，这些结果表明 ccp1 通过促进增殖和抑制细胞死亡来调节细胞数量。FGF2 被证明增强了 ccp1 的作用，但在血清中存在的其他有丝分裂原因子也可能增强 ccp1 的作用。这些作用是否通过 FGF2 影响 ccp1 的功能或通过增加 ccp1 的表达水平来介导仍不清楚。至少 ccp1 的一些增殖调节是通过 MAPK 介导的，但可能还涉及其他信号通路。
