Liao Q, Ozawa F, Friess H, Zimmermann A, Takayama S, Reed J C, Kleeff J, Büchler M W
Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
FEBS Lett. 2001 Aug 17;503(2-3):151-7. doi: 10.1016/s0014-5793(01)02728-4.
Pancreatic cancer cells are usually resistant to apoptosis mediated by intrinsic or extrinsic factors. BAG-3 (Bis, CAIR), which was identified as a BAG-1-related protein, is a novel modulator of cellular anti-apoptotic activity that functions through its interaction with Bcl-2. In this study we analyzed BAG-3 expression in human pancreatic cancer tissues and cell lines. BAG-3 mRNA was expressed at moderate to high levels in all pancreatic cancer samples, but at low levels in normal pancreas tissues. In situ hybridization and immunohistochemistry analysis revealed that BAG-3 was present in the cancer cells within the pancreatic tumor mass. When BAG-3 mRNA was analyzed in other gastrointestinal cancers (hepatocellular carcinoma; esophageal, stomach and colon cancer), no difference was found from their corresponding normal controls. In pancreatic cancer cells, BAG-3 mRNA expression levels were strongly induced after heat stress, but not in response to members of the tumor necrosis factor (TNF)-alpha family (TNF-alpha, TRAIL, FasL). These findings indicate that in pancreatic cancer, in contrast to other gastrointestinal malignancies, increased levels of BAG-3 might function to block apoptosis. This characteristic of pancreatic cancer might contribute to its more aggressive growth behavior and poor responsiveness to treatment in vivo.
胰腺癌细胞通常对由内在或外在因素介导的细胞凋亡具有抗性。BAG-3（双，CAIR）被鉴定为一种与BAG-1相关的蛋白质，是一种新型的细胞抗凋亡活性调节剂，通过与Bcl-2相互作用发挥功能。在本研究中，我们分析了BAG-3在人胰腺癌组织和细胞系中的表达。BAG-3 mRNA在所有胰腺癌样本中呈中度至高水平表达，但在正常胰腺组织中表达水平较低。原位杂交和免疫组织化学分析显示，BAG-3存在于胰腺肿瘤块内的癌细胞中。当分析其他胃肠道癌症（肝细胞癌；食管癌、胃癌和结肠癌）中的BAG-3 mRNA时，与相应的正常对照相比未发现差异。在胰腺癌细胞中，热应激后BAG-3 mRNA表达水平强烈诱导，但对肿瘤坏死因子（TNF）-α家族成员（TNF-α、TRAIL、FasL）无反应。这些发现表明，在胰腺癌中，与其他胃肠道恶性肿瘤不同，BAG-3水平升高可能起到阻止细胞凋亡的作用。胰腺癌的这一特征可能导致其在体内更具侵袭性的生长行为和对治疗的低反应性。
