Hwang Jin-Hyeok, Lee Sang Hyub, Lee Kwang Hyuck, Lee Keung Youp, Kim Haeryoung, Ryu Ji Kon, Yoon Yong Bum, Kim Yong-Tae
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungon-dong Chongno-gu, Seoul 110-744, Republic of Korea.
Cancer Lett. 2009 Jan 18;273(2):266-72. doi: 10.1016/j.canlet.2008.08.028. Epub 2008 Nov 11.
This study investigated the influence of cathepsin B (CATB), a downstream target of Hedgehog (Hh) signaling, in pancreatic cancer. Cyclopamine (Hh signal inhibitor) suppressed expression of Shh, as well as Hh-induced transcription factor Gli1, and induced apoptosis in Shh-positive pancreatic cancer cell line (PANC-1). Microarray analysis revealed CATB as a gene downregulated by Hh. Cyclopamine reduced CATB protein and mRNA levels. Cyclopamine or CATB inhibitor reduced PANC-1 cell invasiveness (P<0.05). CATB expression in human pancreatic cancer tissues tended to correlate with Shh expression (P=0.053). Conclusively, Hh targets CATB and Hh signaling through CATB might influence pancreatic cancer cell invasiveness.
本研究调查了刺猬信号通路（Hh）的下游靶点组织蛋白酶B（CATB）在胰腺癌中的作用。环杷明（Hh信号抑制剂）可抑制音猬因子（Shh）以及Hh诱导的转录因子Gli1的表达，并诱导Shh阳性的胰腺癌细胞系（PANC-1）凋亡。基因芯片分析显示CATB是一个受Hh下调的基因。环杷明可降低CATB的蛋白和mRNA水平。环杷明或CATB抑制剂可降低PANC-1细胞的侵袭能力（P<0.05）。人胰腺癌组织中CATB的表达与Shh的表达呈正相关趋势（P=0.053）。总之，Hh靶向作用于CATB，且通过CATB的Hh信号通路可能影响胰腺癌细胞的侵袭能力。
