Abstract
Background and ObjectivesHuman papillomaviruses have been linked causally to some human cancers such as cervical carcinoma, but there is very little research addressing the effect of HPV infection on human liver cells. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well.MethodsWe applied PCR to detect the possible integration of HPV genes in Hep G2 cells. We also investigated the expression of the integrated E6 and E7 genes by using RT-PCR and Western blotting. Then, we silenced E6 and E7 expression and checked the cell proliferation and apoptosis in Hep G2 cells. Furthermore, we analyzed the potential genes involved in cell cycle and apoptosis regulatory pathways. Finally, we used in situ hybridization to detect HPV 16/18 in hepatocellular carcinoma samples.ResultsHep G2 cell line contains integrated HPV 18 DNA, leading to the expression of the E6 and E7 oncogenic proteins. Knockdown of the E7 and E6 genes expression reduced cell proliferation, caused the cell cycle arrest at the S phase, and increased apoptosis. The human cell cycle and apoptosis real-time PCR arrays analysis demonstrated E6 and E7-mediated regulation of some genes such as Cyclin H, UBA1, E2F4, p53, p107, FASLG, NOL3 and CASP14. HPV16/18 was found in only 9% (9/100) of patients with hepatocellular carcinoma.ConclusionOur investigations showed that HPV 18 E6 and E7 genes can be integrated into the Hep G2, and we observed a low prevalence of HPV 16/18 in hepatocellular carcinoma samples. However, the precise risk of HPV as causative agent of hepatocellular carcinoma needs further study.
Highlights
Epidemiological studies have shown that HPV infection is the main etiological factor for cervical cancer [1] and high-risk HPV type viral DNAs are frequently integrated into the host cell genome in HPV-related cervical carcinomas [2]
This integration has been associated with dysregulation of E6 and E7 viral genes expression, which accounts for the major oncogenic activity of the HPV DNA [3]
In order to characterize the Hep G2 cell line more explicitly, we used the anti-human hepatocyte antibody to verify the characteristics of the hepatoma cells
Summary
Epidemiological studies have shown that HPV infection is the main etiological factor for cervical cancer [1] and high-risk HPV type viral DNAs are frequently integrated into the host cell genome in HPV-related cervical carcinomas [2]. This integration has been associated with dysregulation of E6 and E7 viral genes expression, which accounts for the major oncogenic activity of the HPV DNA [3]. The human hepatoma derived cell line Hep G2 was derived from biopsies taken during extended lobectomy of a 15-year-old Caucasian male from Argentina [5]. We chose the human hepatoma derived cell line Hep G2 to investigate whether HPV gene integration took place in liver cells as well
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
