Roles of Fyn in pancreatic cancer metastasis
Roles of Fyn in pancreatic cancer metastasis
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Fyn 在胰腺癌转移中的作用
DOI：
10.1111/j.1440-1746.2009.06021.x
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发表时间：
2010-02-01
影响因子：
4.1
通讯作者：
Li, Xiao-Wu
中科院分区：
文献类型：
--
作者：
Chen, Zhi-Yu;Cai, Lei;Li, Xiao-Wu
背景和目标：Src家族激酶被认为与肿瘤的转移有关，但其相关机制尚不清楚。本研究的目的是评估可能的机制，通过抑制Fyn激活调节胰腺癌transferation.Methods：我们检测Fyn在人胰腺癌组织中的表达，并系统地研究Fyn表达与胰腺癌转移的关系。采用BxPC 3细胞诱导的裸鼠移植瘤模型，观察抑制Fyn对裸鼠体内转移的影响。采用MTT法和末端脱氧核苷酸转移酶标记法检测Fyn对胰腺癌BxPC 3细胞增殖的影响。结果：Fyn蛋白表达上调与胰腺癌转移密切相关。在BxPC 3胰腺癌细胞中，通过激酶死亡的Fyn转染抑制Fyn活化降低了裸鼠的肝转移。进一步的分析表明，Fyn活性通过调节细胞增殖和凋亡调控胰腺癌细胞的转移。结论：Fyn活性调节细胞增殖和凋亡可能是影响胰腺癌转移的一种机制。
Background and Aims: Src family kinases have been suggested to be associated with the metastasis of tumors, but their related mechanisms remain unclear. The aims of the present study were to assess the possible mechanisms by which the inhibition of Fyn activation regulates pancreatic cancer metastasis.Methods: We examined the expressions of Fyn in human pancreatic cancer tissues by immunohistochemistry and systematically investigated the relationship between Fyn expression and pancreatic cancer metastasis. A nude mouse xenograft model induced by BxPC3 cells with or without the inhibition of Fyn activation was used to explore the effect of the inhibition of Fyn on metastasis in vivo. Methyl thiazolyl tetrazolium and terminal deoxynucleotidyl transferase-labeling assays were used to examine the effect of the inhibition of Fyn on the cell proliferation of BxPC3 pancreatic cancer cells in vitro. Reverse transcription polymerase chain reaction and Western blot analysis were performed to explore the possible mechanism of Fyn-induced metastasis.Results: We found that the upregulation of Fyn expression was correlated with human pancreatic cancer metastasis. In BxPC3 pancreatic cancer cells, the inhibition of Fyn activation by kinase-dead Fyn transfection decreased liver metastasis in nude mice. Further analyses showed that Fyn activity modulated pancreatic cell metastasis through the regulation of proliferation and apoptosis.Conclusions: Our results suggest a possible mechanism by which Fyn activity regulates cell proliferation and apoptosis that exerts an effect on pancreatic cancer metastasis.