Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence.
Pancreatitis-induced inflammation contributes to pancreatic cancer by inhibiting oncogene-induced senescence.
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DOI：
10.1016/j.ccr.2011.05.011
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发表时间：
2011-06-14
期刊：
影响因子：
50.3
通讯作者：
Barbacid M
中科院分区：
文献类型：
--
作者：
Guerra C;Collado M;Navas C;Schuhmacher AJ;Hernández-Porras I;Cañamero M;Rodriguez-Justo M;Serrano M;Barbacid M
成年小鼠 (≥P60) 的胰腺腺泡细胞对一些最强烈的致癌损伤的转化具有抵抗力，包括 K-Ras 癌基因的表达和 p16Ink4a/p19Arf 或 Trp53 肿瘤抑制因子的丧失。然而，如果这些腺泡细胞暴露于有限的非急性胰腺炎，只要它们含有 K-Ras 癌基因，就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 的衰老屏障特征来促进肿瘤进展。胰腺炎引起的炎症的减弱也会加速组织修复并阻止 mPanIN 扩张。如果慢性胰腺炎患者接受过抗炎药物治疗，他们会出现 PanIN 衰老现象。这些结果提出了这样的概念：对诊断为胰腺炎的人进行抗炎治疗可能会降低他们患 PDAC 的风险。
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, if they have received anti-inflammatory drugs. These results put forward the concept that anti-inflammatory treatment of people diagnosed with pancreatitis may reduce their risk of developing PDAC.