胰腺炎引发的炎症通过抑制致癌基因诱导的衰老促进胰腺癌的发生。
Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence.
机构信息
Experimental Oncology, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
出版信息
Cancer Cell. 2011 Jun 14;19(6):728-39. doi: 10.1016/j.ccr.2011.05.011.
Abstract
Pancreatic acinar cells of adult mice (≥P60) are resistant to transformation by some of the most robust oncogenic insults including expression of K-Ras oncogenes and loss of p16Ink4a/p19Arf or Trp53 tumor suppressors. Yet, these acinar cells yield pancreatic intraepithelial neoplasias (mPanIN) and ductal adenocarcinomas (mPDAC) if exposed to limited bouts of non-acute pancreatitis, providing they harbor K-Ras oncogenes. Pancreatitis contributes to tumor progression by abrogating the senescence barrier characteristic of low-grade mPanINs. Attenuation of pancreatitis-induced inflammation also accelerates tissue repair and thwarts mPanIN expansion. Patients with chronic pancreatitis display senescent PanINs, providing they have received antiinflammatory drugs. These results support the concept that antiinflammatory treatment of people diagnosed with pancreatitis may reduce their risk of developing PDAC.
摘要
成年小鼠（≥P60）的胰腺腺泡细胞对一些最强大的致癌侵袭具有抗性，包括表达 K-Ras 癌基因和缺失 p16Ink4a/p19Arf 或 Trp53 肿瘤抑制基因。然而，如果这些腺泡细胞携带 K-Ras 癌基因，并暴露于有限的非急性胰腺炎发作中，它们会产生胰腺上皮内瘤变（mPanIN）和导管腺癌（mPDAC）。胰腺炎通过消除低级别 mPanIN 特征性的衰老屏障促进肿瘤进展。减轻胰腺炎引起的炎症也会加速组织修复并阻止 mPanIN 的扩张。患有慢性胰腺炎的患者如果接受了抗炎治疗，会出现衰老的 PanIN。这些结果支持这样一种概念，即对诊断患有胰腺炎的人进行抗炎治疗可能会降低他们患 PDAC 的风险。
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