Androgen Receptor Is a New Potential Therapeutic Target for the Treatment of Hepatocellular Carcinoma

Abstract

Our data point to AR, but not androgens, as a potential new and better therapeutic target for the battle of HCC.

Identification of androgen response elements in the enhancer I of hepatitis B virus: A mechanism for sex disparity in chronic hepatitis B

“…Because the occurrence of chemically induced liver cancer is delayed in AR knockout mice, AR itself clearly behaves as a tumor-promoting gene for HCC. 7 Our previous study showed that HBx could enhance the transcriptional activity of AR, which leads to an increased risk of HCC. 8 The current study further disclosed a new role of AR in liver carcinogenesis, namely the activation of HBV transcription and replication.…”

“…5,6 In AR knockout mice, the development of chemically induced HCC was delayed and the mice had fewer tumors. 7 These studies indicate that the AR axis is involved in hepatocarcinogenesis, and an active AR pathway may augment HCC risk. Consistent with this, we recently showed that HBV X protein (HBx) can enhance the transcriptional activity of AR in a ligand concentration-dependent manner, which may explain the male predominance of HBV-related HCC.…”

Androgen Receptor and Hepatocellular Carcinoma

“…The androgen pathway can increase the transcription of HBV through direct binding to the ARE sites in HBV enhancer I, leading to a higher HBV titer in male carriers and increased risk of HCC [53]. These facts together suggest that the targeting of AR might be developed as a new therapeutic strategy against HBV-related HCC [54].…”

“…Ma et al [54] reported that mice lacking hepatic AR developed later and less HCC than their wild-type littermates with comparable serum testosterone in both males and females when using the Cre-Lox conditional knockout mouse model injected with carcinogen and that AR may promote hepatocarcinogenesis via increased cellular oxidative stress and DNA damage, as well as by suppression of p53-mediated DNA damage sensing/repairing system and cell apoptosis. Recently, it has been shown that vertebrae forkhead box A (Foxa) factors and their targets estrogen receptor (ERα) and/or AR play an important role in the sexual dimorphism of HCC [55].…”

The Rats Liver External Secretory Function in Blockade of Androgen Receptors With Flutamide

“…Ймовірна участь тестостерону у цих процесах підтвер-джується наявністю рецепторів андрогенів у гепатоцитах і холангіоцитах [4][5][6]. Дійсно, кастрація щурів або нейтралізація цирку-люючого тестостерону антитілами зменшує масу печінкових проток, викликає апоптоз холангіоцитів, а замісне його введення перешкоджає їх загибелі [6].…”