MDM4 expression in fibrolamellar hepatocellular carcinoma

Oncology Reports
Anju KarkiKhashayar Vakili

Abstract

Fibrolamellar hepatocellular carcinoma (FL‑HCC) is a variant of hepatocellular carcinoma (HCC) that most commonly affects adolescents and young adults and is associated with an extremely poor prognosis due to the lack of effective chemotherapeutic agents. Mutations in p53 are a common oncogenic driver in HCC but not in FL‑HCC. However, in tumors lacking a p53 mutation, the tumor suppressor activity of p53 has been revealed to be dysregulated in several different cancer types. One mechanism has been attributed to the overexpression of mouse double minute 4 protein (MDM4), a negative regulator of p53, which inhibits the normal functions of p53 including induction of apoptosis and DNA repair. Therefore, restoring the normal function of p53 in cancer cells by targeting MDM4 has become a potential therapeutic strategy. Hence, in the present study the components of the DNA damage response (DDR) pathway were examined; ATM, p53, and MDM4 in FL‑HCC. Seven FL‑HCC tumors along with their adjacent non‑neoplastic hepatic tissues were examined. Ataxia‑telangiectasia mutated (ATM), p53, and MDM4 protein expression was assessed using western blot analysis and cellular localization was determined using immunohistochemistry (IHC). MDM4 mRNA tran...Continue Reading

Citations

Aug 28, 2020·Frontiers in Oncology·De-Hua YuJiang-Jiang Qin

Related Concepts

Antineoplastic Agents
Ataxia Telangiectasia
Western Blotting
Malignant Neoplasms
Cell Nucleus
Cytoplasm
DNA Damage
Immunohistochemistry
Laboratory mice
Neoplasms

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