Hypermethylation of SOX2 Promoter in Endometrial Carcinogenesis

Abstract

This paper aimed at investigating the expression and methylation profiles of SOX2, a gene coding for the stem cell-related transcription factor SOX2, in endometrial carcinomas. By methylation-specific polymerase chain reaction (MS-PCR), the methylation status of SOX2 promoter region in 72 endometrial carcinomas and 12 normal endometrial samples was examined. Methylated allele was found in 37.5% (27/72) of endometrial carcinomas but only in 8.3% (1/12) of normal endometrial, significantly more frequent in cancers (P = .0472). SOX2 mRNA level was significantly reduced in endometrial carcinoma compared with nonneoplastic endometrium (P = .045). A significant correlation between SOX2 mRNA expression and hypermethylation of SOX2 was found (P = .024). Hypermethylation of SOX2 tended to be more frequently found in type II serous or clear cell adenocarcinoma. SOX2 methylation was also significantly correlated with shorter survival of patients (P = .046). In conclusion, epigenetic mechanisms may play a crucial role on the transcriptional regulation of SOX2 and loss of SOX2 expression may be related to endometrial carcinogenesis.

Effects on specific promoter DNA methylation in zebrafish embryos and larvae following benzo[a]pyrene exposure

“… 1 References: apc (Richiardi et al, 2013; Heller et al, 2010; Hernandez-Vargas et al, 2010); bdnf (D’Addario et al, 2012; Fuchikami et al, 2011; Keller et al, 2010; Autry and Monteggia, 2009); brca1 (Esteller et al, 2000; Esteller et al, 2001; Xu et al, 2009); cdh2 (Berx and van Roy 2009; Sui et al, 2012; Loo et al, 2010); cdkn1a (Campion et al, 2009); c-fos (Liu et al, 2003; Wainfan and Poirier, 1992); cyp1b1 (DiNardo et al, 2013; Habano et al, 2009; Sissung et al, 2006; Tokizane et al, 2005); dazl (Li et al, 2013; Krausz et al, 2012; Navarro-Costa et al, 2010); drd2l (Abdolmaleky et al, 2005); esr1 (Majumdar et al, 2011; Campion et al, 2009); gstp1 (Richiardi et al, 2013; Muggerud et al, 2010); h-ras (Hass et al, 1993; Campion et al, 2009); mlh1 (Muggerud et al, 2010; Heller et al, 2010; Esteller et al, 2001); msh3 (Lahtz and Pfeifer, 2011); nos2b (Breton et al, 2012); nqo1 (Tada et al, 2005); nrf2 (Khor et al, 2011; Yu et al, 2010); p53 (Intarasunanont et al, 2012; Zeng et al, 2011; Hernandez-Vargas et al, 2010; Campion et al, 2009); pten (Campion et al, 2009; Muggerud et al, 2010); sox2 (Farthing et al, 2008; Wong et al, 2010; Hirabayashi and Gotoh, 2010); sox3 (Hirabayashi Gotoh, 2010). …”

Sox2‐dependent inhibition of p21 is associated with poor prognosis of endometrial cancer

“…In most types of cancers, SOX2 acts as an oncogenic transcriptional factor, and thus it may become a novel therapeutic target in these cancers . However, the roles of SOX2 in endometrial cancer are still unclear …”

Sex-determining region Y box-containing genes: regulators and biomarkers in gynecological cancers

“…High expression level of SOX2 in tissues was also associated with poorer outcomes of patients with advanced-stage EC 11 . In contrast, Wong et al 58 proposed that SOX2 was a tumor suppressor gene inhibiting the progression of EC, and low level of it was identified as an indicator of type II serous, clear cell adenocarcinoma as well as shorter survival. These phenomena suggested that further exploration of the molecular mechanisms of SOX2 should be carried out in relation to clinical management of EC.…”

“…Overexpression of SOX2 in cells promoted cell proliferation by inhibiting expression of p21 11 , while low level of SOX2 in tissues caused by promoter hyper-methylation was conversely accompanied by initiation of EC 58 . These phenomena reflecting the role of SOX2 as a biomarker of clinical features in patients with EC was possibly due to different locations of SOX2 and its currently unclear mechanisms.…”

“…Despite extensive research focusing on exploring the genetic and epigenetic characteristics of EC, its pathogenesis and progression remain unclear. Recently, some studies indicated the important roles for SOX genes in regulating the progression of EC ( Figure 6 ) and in indicating clinical features and treatment efficacy of patients with EC ( Table 1 ) 19,21,58,71,72 . …”