Author/Authors :
Sadeghizadeh Majid نويسنده , Mokhtari Azad Talat نويسنده , Faghihloo Ebrahim نويسنده Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran , Shahmahmoodi Shohreh نويسنده Department of Virology, School of Public Health, Tehran
University of Medical Sciences, Tehran, IR Iran
Abstract :
Background Cervical cancer is one of the most common cancers
observed in women worldwide, and its development is related to E6 and E7
two viral oncoproteins of high-risk human papillomavirus (HPV) types.
Aberrant expression of E-cadherin, which is associated with
epithelial-to-mesenchymal transition (EMT), is frequently observed in
cervical cancer. Objectives The mechanisms underlying E-cadherin
suppression in cervical cancer are not clear; therefore, this
experimental study from Iran was designed to elucidate the relationship
of DNA methyltransferase expression and E-cadherin promoter methylation
with E-cadherin expression in HPV-16 E6- and E7-expressing cells.
Materials and Methods Real-time PCR and western blot were used to
determine the effects of HPV-16 E6 and E7 on E-cadherin, DNMT1, DNMT3a,
and DNMT3b expression in HCT-116 cell line. We also analyzed E-cadherin
promoter methylation in cells expressing HPV-16 E6 and E7 oncoproteins
by bisulfite sequencing. Results HPV-16 E6 and E7 proteins reduced
E-cadherin expression 3.7 and 2.2 times when compared with control cells
(P = 0.0221 and P = 0.0461, respectively). This reduction was greater in
HPV-16 E6-expressing cells than in HPV-16 E7-expressing cells. Although
HPV-16 E6 and E7 increased DNA methyltransferase 1 expression 2.6 and
3.4 times, respectively (P = 0.0133 and P = 0.0113) when compared with
control cells, they was no E-cadherin promoter methylation. Conclusions
Unlike other cancer-associated viruses (HBV, HCV, and EBV), reduction in
E-cadherin expression in HPV-16 E6- and E7-expressing cells is not due
to hypermethylation of the E-cadherin promoter.
