Gene interactions and pathways from curated databases and text-mining
Hepatology 2009, PMID: 19475690

Enhanced expression of vascular endothelial growth factor-A in ground glass hepatocytes and its implication in hepatitis B virus hepatocarcinogenesis.

Yang, Jui-Chu; Teng, Chiao-Fang; Wu, Han-Chieh; Tsai, Hung-Wen; Chuang, Huai-Chia; Tsai, Ting-Fen; Hsu, Yung-Hsiang; Huang, Wenya; Wu, Li-Wha; Su, Ih-Jen

Ground glass hepatocytes (GGH) in chronic hepatitis B virus (HBV) infection harbor HBV pre-S deletion mutants in endoplasmic reticulum (ER) and exhibit complex biologic features such as ER stress, DNA damage, and growth advantage. The presence of pre-S mutants in serum has been shown to predict the development of hepatocellular carcinoma (HCC) in HBV carriers. GGHs hence represent a potentially preneoplastic lesion. Whether a specific growth factor is overexpressed and activated in GGHs remains to be clarified. In this study, growth factor(s) up-regulated by pre-S mutants was identified using a growth factor array in HuH-7 cells. Immunohistochemistry, reverse-transcriptase polymerase chain reaction, and Western blot analysis were performed to study the participation of these genes and their signal pathways in HuH-7 cells and liver tissues. We demonstrate that vascular endothelial growth factor-A (VEGF-A) was up-regulated by pre-S mutants in HuH-7 cells and further confirmed in GGHs by immunostaining. The VEGF-A up-regulation by pre-S mutants could be suppressed by vomitoxin, an ER stress inhibitor. Furthermore, pre-S mutants-expressed HuH-7 cells exhibited activation of Akt/mTOR (mammalian target of rapamycin) signaling and increased growth advantage, which could be inhibited by VEGF-A neutralization. Consistent with this notion, enhanced expression of VEGF-A and activation of Akt/mTOR signaling, comparable to the levels of paired HCC tissues, were also detected in HBV-related nontumorous livers.

CONCLUSIONS

The enhanced expression of VEGF-A in GGHs provides potential mechanism to explain the progression from preneoplastic GGHs to HCC in chronic HBV infection.

Diseases/Pathways annotated by Medline MESH: Liver Neoplasms
Document information provided by NCBI PubMed

Text Mining Data

VEGF-A → Akt/mTOR signaling: " Consistent with this notion, enhanced expression of VEGF-A and activation of Akt/mTOR signaling , comparable to the levels of paired HCC tissues, were also detected in HBV related nontumorous livers "

VEGF-A → Akt/mTOR: " Consistent with this notion, enhanced expression of VEGF-A and activation of Akt/mTOR signaling, comparable to the levels of paired HCC tissues, were also detected in HBV related nontumorous livers "

Manually curated Databases

No curated data.