MUC4 mucin potentiates pancreatic tumor cell proliferation, survival, and invasive properties and interferes with its interaction to extracellular matrix proteins
MUC4 mucin potentiates pancreatic tumor cell proliferation, survival, and invasive properties and interferes with its interaction to extracellular matrix proteins
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DOI：
10.1158/1541-7786.mcr-06-0353
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发表时间：
2007-04-01
影响因子：
5.2
通讯作者：
Batra, Surinder K.
中科院分区：
文献类型：
--
作者：
Chaturvedi, Pallavi;Singh, Ajay P.;Batra, Surinder K.
MUC4是一种跨膜粘蛋白，在胰腺癌中异常表达，而在正常胰腺组织中检测不到。最近的研究表明，MUC4的表达与胰腺癌的进展有关，与胰腺癌患者的预后呈负相关。在本研究中，我们研究了MUC4沉默的表型和分子后果，目的是建立其在胰腺癌发病机制中观察到的作用的机制基础。在高转移性胰腺癌细胞CD18/HPAF中稳定表达MUC4短发夹状RNA，实现了MUC4表达的沉默。免疫印迹分析和免疫荧光共聚焦显微镜检测到MUC4基因敲除(CD18/HPAF-siMUC4)细胞的MUC4表达明显低于亲本细胞和杂交短干扰RNA(CD18/HPAF-SCR)对照细胞。与我们之前的观察一致，抑制MUC4的表达抑制了胰腺癌细胞的生长和转移，如在原位小鼠模型中所显示的那样。我们的体外研究表明，MUC4相关的肿瘤细胞生长的增加是由于促进了增殖和减少了细胞死亡。此外，MUC4的表达还与显著增加的侵袭性相关(P
MUC4, a transmembrane mucin, is aberrantly expressed in pancreatic adenocarcinomas while remaining undetectable in the normal pancreas. Recent studies have shown that the expression of MUC4 is associated with the progression of pancreatic cancer and is inversely correlated with the prognosis of pancreatic cancer patients. In the present study, we have examined the phenotypic and molecular consequences of MUC4 silencing with an aim of establishing the mechanistic basis for its observed role in the pathogenesis of pancreatic cancer. The silencing of MUC4 expression was achieved by stable expression of a MUC4-specific short hairpin RNA in CD18/HPAF, a highly metastatic pancreatic adenocarcinoma cell line. A significant decrease in MUC4 expression was detected in MUC4-knockdown (CD18/HPAF-siMUC4) cells compared with the parental and scrambled short interfering RNA-transfected (CD18/HPAF-Scr) control cells by immunoblot analysis and immunofluorescence confocal microscopy. Consistent with our previous observation, inhibition of MUC4 expression restrained the pancreatic tumor cell growth and metastasis as shown in an orthotopic mouse model. Our in vitro studies revealed that MUC4-associated increase in tumor cell growth resulted from both the enhanced proliferation and reduced cell death. Furthermore, MUC4 expression was also associated with significantly increased invasiveness (P