Li Jun, Gu Zhuoyu, Li Siyuan, Xiao Zhiwei, Sun Kan
Department of Endocrinology, First Affiliated Hospital, Medical School of Shihezi University Shihezi 832002, China.
Key Laboratory of Ministry of Education, Xinjiang Endemic and Ethnic Diseases, Medical College of Shihezi University Shihezi 832002, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9279-85. eCollection 2015.
Steps in the genetic basis of pancreatic cancer (PC) have been recently identified, however, Studies focusing on the relationship between Jab1 and Smad4 in PC are rarely reported. This study was performed to examine the expression patterns and association of Jab1 and Smad4 in PC cells for gaining a further understanding of PC pathogenesis.
Human pancreatic cancer cell line PANC-1 cells were infected with retrovirus vector containing GFP, HA-Jab1, siGFP, and siJab1 respectively. The expression of Jab1 and Smad4 in PANC-1 cells was analyzed by Western blot and immunocytochemistry. Subsequently, the effect of overexpression of Jab1 on cell proliferation inhibition mediated by TGF-β was examined with MTT colorimetry.
The expression of Smad4 in PANC-1 cells was inhibited after the overexpression of Jab1. Inversely, the expression of Smad4 was increased after the down-regulation of Jab1 silenced by SiRNA. Smad4 expression in PANC-1 cells was negatively correlated with Jab1 expression. In addition, the cell proliferation inhibitory effect induced by TGF-β in PANC-1 cells was attenuated after the overexpression of Jab1.
The reverse correlation of Jab1 and Smad4 in PANC-1 cells may be involved in the Pathogenesis of PC. Jab1 can cause degradation of Smad4 via TGF-β signal pathway, consequently contributing to the proliferation of PC cells.
胰腺癌（PC）的遗传基础相关步骤最近已被确定，然而，聚焦于Jab1与Smad4在PC中关系的研究鲜有报道。本研究旨在检测Jab1和Smad4在PC细胞中的表达模式及相关性，以进一步了解PC的发病机制。
分别用含绿色荧光蛋白（GFP）、HA-Jab1、siGFP和siJab1的逆转录病毒载体感染人胰腺癌细胞系PANC-1细胞。采用蛋白质免疫印迹法和免疫细胞化学法分析PANC-1细胞中Jab1和Smad4的表达。随后，用MTT比色法检测Jab1过表达对TGF-β介导的细胞增殖抑制作用的影响。
Jab1过表达后，PANC-1细胞中Smad4的表达受到抑制。相反，通过小干扰RNA（SiRNA）沉默Jab1后，Smad4的表达增加。PANC-1细胞中Smad4的表达与Jab1的表达呈负相关。此外，Jab1过表达后，TGF-β诱导的PANC-1细胞增殖抑制作用减弱。
PANC-1细胞中Jab1与Smad4的负相关可能参与了PC的发病机制。Jab1可通过TGF-β信号通路导致Smad4降解，从而促进PC细胞的增殖。
