p53 protects against formation of extrahepatic biliary precancerous lesions in the context of oncogenic Kras

• Published in: Oncotarget Vol. 14; no. 1; pp. 276 - 279
• Main Authors: Nagao, Munemasa, Mizukoshi, Kenta, Nakayama, Shinnosuke, Namikawa, Mio, Hiramatsu, Yukiko, Maruno, Takahisa, Nakanishi, Yuki, Tsuruyama, Tatsuaki, Fukuda, Akihisa, Seno, Hiroshi
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 31-03-2023
• Subjects: Animals; Bile Duct Neoplasms - genetics; Bile Duct Neoplasms - pathology; Bile Duct Neoplasms - prevention & control; Bile Ducts, Extrahepatic - pathology; Bile Ducts, Intrahepatic - pathology; Biliary Tract Neoplasms - pathology; Cholangiocarcinoma - pathology; Mice; Precancerous Conditions - genetics; Precancerous Conditions - pathology; Proto-Oncogene Proteins p21(ras) - genetics; Proto-Oncogene Proteins p21(ras) - metabolism; BilIN; ICPN; Kras; biliary cancer; p53
• ISSN: 1949-2553; 1949-2553
• 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.