Gallbladder cancer - gene expression profiling

• Enhanced expression of trophinin promotes invasive and metastatic potential of human gallbladder cancer cells

Journal of Cancer Research & Clinical Oncology (2009) volume: 135 issue: 4 page: 581

Xin-Zhong Chang, Jie Yu, Xue-Hui Zhang, Jian Yin, Tao Wang and Xu-Chen

Abstract

Purpose:
To study effects of trophinin on the metastatic potential of human gallbladder cancer cells and its potential mechanism.

Materials And Methods:
Expression of trophinin in the highly metastatic GBC-SDHi cells was investigated by real time RT-PCR and western blot. Recombinant expression plasmid vector of the human trophinin gene was constructed and transfected into GBC-SD cells. Effects of trophinin on the invasion of GBC-SD cells were investigated by adhesion assay and invasion assay in vitro. The siRNA was used to down-regulate the expression of trophinin. Some genes related to the invasion and metastasis of cancer were determined by real time RT-PCR and western blot. The pulmonary metastasis regulated by trophinin was determined in the nude mice.

Results:
Overexpression of trophinin in GBC-SDHi cells was confirmed compared with its parental counterparts. Up-regulation of trophinin enhanced the in vitro invasion in the GBC-SD/TRO cells. The enhancement was associated with increasing integrin α3, MMP-7, MMP-9, and Ets-1 expression. The results were further demonstrated by RNA interference experiment in vitro. In in vivo study, we also demonstrated that trophinin-transfected gallbladder cancer cells had more pulmonary metastases than the vector-transfected one or its parental counterparts.

Conclusion:
Overexpression of trophinin leads to a more invasive phenotype and metastatic potential in human gallbladder cancer, at least in part, through regulating integrin α3, MMP-7, MMP-9, and Ets-1 expression.

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