Background: To explore the potential therapeutic target to treat pancreatic cancers, Tspan1 was detected in human pancreatic cancer tissue and human pancreatic ductal adenocarcinoma cells and functional role of Tspan1 on proliferation was explored and the mechanism was investigated. Materials and Methods: Tspan1 in PCC tissue and PDAC cell lines was measured by qRT-PCR and Western blot. Tspan1 was knock-downed and over-expressed in cells via transfection with Tspan1-siRNA and pLNCX-TSPAN1-cDNA, cell survival, proliferation and cell cycle were measured with MTT, Alamar blue and Flow Cytometry assay. The mRNA and protein expression were assessed by qRT-PCR and Western blotting. The expression of PI3K, Akt and p-Akt were detected, and CDK1 siRNA and specific inhibitor of Akt were used to explore the mechanism of TSPAN1 promoting PDAC cells proliferation. Results: Tspan1 expression in PCC tissue and PDAC cells was increased. Transfection of siRNA targeting Tspan1 in BxPC3 and PNAC-1 cells obviously decreased cell proliferation and down-regulated CDK1 expression. Consistently, both cell proliferation and CDK1 expression in BxPC3 and PNAC-1 cells were up-regulated with pLNCX-TSPAN1-cDNA transfection. Cell cycle analysis showed that after knockdown of Tspan1 the G2/M phase ratio was increased to cause mitosis arrest, and TSPAN1 overexpression caused cell cycle transition from G2 to M phase to promote cell proliferation. And these were dependent on the modulation of CDK1 expression via Akt. Conclusion: Tspan1 up-regulates CDK1 expression via activating Akt to promote human PCC cell proliferation and silencing of Tspan1 may be a potential therapeutic target to treat pancreatic cancers.

中文翻译：

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TSPAN1通过通过Akt调节CDK1促进人胰腺癌细胞的增殖

背景：为探讨治疗胰腺癌的潜在靶点，在人胰腺癌组织和人胰导管腺癌细胞中检测到Tspan1，并探讨了Tspan1对增殖的作用，并研究了其机制。材料和方法：通过qRT-PCR和Western blot检测PCC组织和PDAC细胞系中的Tspan1。通过用Tspan1-siRNA和pLNCX-TSPAN1-cDNA转染，Tspan1被敲低并在细胞中过表达，MTT，Alamar蓝和流式细胞术检测了细胞存活，增殖和细胞周期。通过qRT-PCR和Western印迹评估mRNA和蛋白质表达。检测PI3K，Akt和p-Akt的表达，为了研究TSPAN1促进PDAC细胞增殖的机制，使用了CDK1 siRNA和Akt的特异性抑制剂。结果：Tspan1在PCC组织和PDAC细胞中的表达增加。在BxPC3和PNAC-1细胞中转染靶向Tspan1的siRNA明显降低了细胞增殖并下调了CDK1表达。一致地，pLNCX-TSPAN1-cDNA转染可同时上调BxPC3和PNAC-1细胞中的细胞增殖和CDK1表达。细胞周期分析表明，敲低Tspan1后，G2 / M期比例增加，导致有丝分裂停滞，TSPAN1过表达导致细胞周期从G2期过渡到M期，从而促进细胞增殖。这些都依赖于通过Akt对CDK1表达的调节。结论：