The C-Terminus of Hepatitis B Virus-encoded X Protein Is Required for Lapatinib Sensitivity in Hepatocellular Carcinoma Cells.

Abstract:

BACKGROUND/AIM:Hepatitis B virus-encoded X protein (HBx) plays a pivotal role in hepatocellular carcinoma (HCC) progression and treatment resistance. Interestingly, our previous study unexpectedly showed that full-length HBx sensitized HCC cells to lapatinib by up-regulating erb-b2 receptor tyrosine kinase 3 (ERBB3). We further aimed to map the exact motif within the HBx sequence responsible for lapatinib sensitization. MATERIALS AND METHODS:The exact motif responsible for the lapatinib sensitization was assessed by construction of various fragments of HBx. Cell viability was examined by the MTT assay and crystal violet staining. RESULTS:Our investigation found that lapatinib sensitivity and up-regulation of ERBB3 promoter activity were observed only in HCC cells expressing C-terminal residues of HBx. Furthermore, C-terminal HBx peptide induced ERBB3 protein expression and sensitivity to lapatinib. CONCLUSION:These results not only indicate that the C-terminus of HBx is required for lapatinib sensitivity, but also provide clues to developing a predictive biomarker for response of HCC to lapatinib in the future.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Chen JY,Huang WC,Wei CT,Chien PH,Chen YJ

doi

10.21873/anticanres.13168

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

721-726

issue

2

eissn

0250-7005

issn

1791-7530

pii

39/2/721

journal_volume

39

pub_type

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