Abstract
Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.
Highlights
Ovarian cancer is a lethal tumor of female genital tract (Siegel et al, 2012)
This study investigated mechanisms of Secreted frizzled-related protein (SFRP) and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus
This study investigated the mechanism for SFRPs and adenomatous polyposis coli (APC) genes loss in ovarian cancer infected with high risk human papillomavirus
Summary
Ovarian cancer is a lethal tumor of female genital tract (Siegel et al, 2012). Its incidence is high in developed countries, with rates exceeding 9/100,000 women per year with 5-year survival rate of 15-20% due to chemoresistance (Ozdemir et al, 2012). Human papillomavirus (HPV) is considered as one of the environmental factors causing ovarian cancer worldwide (Malisic et al, 2012; Shanmughapriya et al, 2012). The activation member of the Wnt pathway leads to inhibition of tumor cell apoptosis in several human cancers (Fonar et al, 2011; Lu et al, 2011; Pacheco-Pinedo et al, 2011). This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. Results: The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. Conclusion: This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation
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