Moderate Activation of the Apoptosis Inhibitor bcl-xL Worsens the Prognosis in Pancreatic Cancer

作者：Helmut Frieß, Lu Zhao, Åke Andrén‐Sandberg, Pascal O. Berberat, Arthur Zimmermann, Guido Adler, Roland M. Schmid, Markus W. Büchler · 发表于：Annals of Surgery · 年份：1998 · DOI：10.1097/00000658-199812000-00009 · 被引用次数：117 · 研究领域：Cell death mechanisms and regulation、Cancer Mechanisms and Therapy、Phagocytosis and Immune Regulation

OBJECTIVE: To analyze the expression of the antiapoptotic gene bcl-xL in human pancreatic cancer and to correlate the results with clinical patient parameters. SUMMARY BACKGROUND DATA: Bcl-xL belongs to the bcl-2-related gene family and acts as a broad antiapoptotic factor to extend both normal and tumor cell survival. Recent findings indicate that tumor cell death induced by chemotherapy and radiotherapy is mediated by the activation of apoptosis. The fact that pancreatic cancer has an extremely malignant potential and that it is resistant to most anticancer treatment modalities suggests that mechanisms are activated that increase the viability of pancreatic cancer cells. METHODS: Seventy-four pancreatic cancer tissue samples were obtained from 32 female and 42 male patients undergoing surgery for exocrine pancreatic cancer. Normal human pancreatic tissue samples were available from 11 organ donors and 4 patients without pancreatic disease. The levels of bcl-xL mRNA expression were analyzed by Northern blot analysis. The exact site of bcl-xL mRNA transcription was determined by nonradioactive in situ hybridization. In addition, immunohistochemistry using specific polyclonal antibodies was used to localize the protein. RESULTS: Northern blot analysis indicated that, in comparison with the normal pancreas, bcl-xL mRNA was markedly overexpressed in 54% of the pancreatic cancer samples. Densitometric analysis revealed that pancreatic adenocarcinomas exhibited a mean 3.4-fold inc...