Publication: HBx-induced androgen receptor
expression in HBV-associated hepatocarcinoma is
independent of the methylation status of its promoter
Authors
Zhu, Rong ; Zhang, Jian-Sheng ; Zhu, Ya-Zhen ; Fan, Jia ; Mao, Yi ; Chen, Qi ; Zhu, Zhu
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Publisher
Murcia: F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
A remarkable feature of HBV-associated
HCC is male predominance. The cooperation of hepatitis
B virus X protein (HBx) with androgen receptor (AR)
signaling pathway has been documented to contribute to
this dominance. HBx, a multifunctional viral regulator,
has been documented to induce promoter
hypermethylation and low expression of tumor
suppressor genes via activation of DNA methyltransferase
(DNMT) in hepatocarcinogenesis. In prostate
cancer, hypermethylation of AR promoter is associated
with loss of AR expression. However, the relationship
among HBx, DNMTs, the methylation status of AR and
AR expression in HBV-associated HCC is still unknown.
In this report, we found that HBx correlated with high
levels of AR in HCC cases and induced AR expression
by stimulating its transcription in liver cell lines. HBx
correlated with high expression of DNMTs in HCC cases
too. Both in vivo and in vitro, however, the expression of
AR was not associated with its promoter methylation
status, and the methylation status of AR was not
regulated by DNMTs. AR expression is higher in
peritumoral tissues than in tumors, as well as being
higher in HBV-associated HCC than in HBV-negative
cases. Therefore, HBx-induced high expression of AR
plays a role during hepatocarcinogenesis, but is not
involved with its promoter methylation or DNMTs.
HBx-mediated DNMT deregulation is gene-specific, and
the expression and methylated regulation of AR is
tissue-specific.
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