Oncotarget. 2023 Mar 31;14:276-279. doi: 10.18632/oncotarget.28380.
and mutations are frequently observed in extrahepatic biliary cancer. Mutations of and are independent risk factors for poor prognosis in biliary cancer. However, the exact role of p53 in the development of extrahepatic biliary cancer remains elusive. In this study, we found that simultaneous activation of Kras and inactivation of p53 induces biliary neoplasms that resemble human biliary intraepithelial neoplasia in the extrahepatic bile duct and intracholecystic papillary-tubular neoplasm in the gall bladder in mice. However, inactivation of p53 was not sufficient for the progression of biliary precancerous lesions into invasive cancer in the context of oncogenic Kras within the observation period. This was also the case in the context of additional activation of the Wnt signaling pathway. Thus, p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras.
并且突变在肝外胆管癌中经常观察到。 和 的突变是胆管癌预后不良的独立危险因素。然而，p53 在肝外胆管癌发展中的确切作用仍不清楚。在这项研究中，我们发现 Kras 的同时激活和 p53 的失活诱导胆管肿瘤，在小鼠的肝外胆管中类似于人类胆管上皮内瘤变，在胆囊中类似于腔内乳头状管状肿瘤。然而，在致癌 Kras 背景下，p53 的失活不足以使胆管癌前病变进展为浸润性癌。在 Wnt 信号通路的额外激活的情况下也是如此。因此，p53 在致癌 Kras 的背景下保护肝外胆管癌前病变的形成。
