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

Abstract

Sex‐determining region Y‐box 2 (SOX2) is an essential factor involved in the self‐renewal and pluripotency of embryonic stem cells and has functions in cell survival and progression in many types of cancers. Here, we found that several endometrial cancer cell lines expressed SOX2, which was required for cell growth. Additionally, SOX2 overexpression regulated the expression of cyclin‐dependent kinase inhibitor 1A (CDKN1A), and SOX2 specifically bound to p21 promoter DNA in endometrial cancer cell lines expressing SOX2. Expressions of SOX2 in endometrial cancer patients were significantly correlated with histological grade and poor prognosis. Moreover, low p21 together with high SOX2 expressions in advanced endometrial cancer patients were associated with the most unfavorable outcomes of patients. These results indicated that simultaneous measurement of SOX2 and p21 expression in endometrial cancer patients may be a useful biomarker for patient prognosis.

Novel MXD4–NUTM1 fusion transcript identified in primary ovarian undifferentiated small round cell sarcoma

“…In addition, immunohistochemical staining for the NUTM1 protein was performed as previously reported 14, 26. Briefly, after deparaffinization, antigen retrieval was performed with Target Retrieval Solution (10 mM citrate buffer, pH 6.0; Dako) in a microwave for 30 minutes at 96°C.…”

“…Western blotting experiments for NUTM1 (C52B1, Cell signaling technology; dilution ratio 1:1000) and anti-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) antibody, clone 6C5 (MAB374, Merck Millipore Headquarters; dilution ratio 1:1000) were performed as previously reported. 13,14,26 Tissues were lysed in RIPA buffer (50 mM Tris at pH 8.0, 150 mM NaCl, 1% Nonidet P-40, 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate [SDS], and 1 mM EDTA) supplemented with protease inhibitors (Roche). The lysates were separated by SDS-polyacrylamide gel electrophoresis on 5%-20% gradient gels and transferred to polyvinylidene difluoride (PVDF) membranes (Millipore).…”

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

“…Pityński et al 15 analyzed expression level of SOX2 in samples from EC patients and found higher expression level of it in high-grade (G3) compared with moderate-grade (G2) and low-grade (G1) of EC. 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.…”

“…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.…”

“…Due to the increased morbidity and mortality of gynecological cancers (GCs) year by year, the roles of SOX genes in GCs, including ovarian (OC), cervical (CC), and endometrial cancer (EC) become a recent focus of researches 5 . Studies investigating the relationship between aberrant expression of SOX genes and the development of GCs found that some SOX genes with high expression level were expected to act as oncogenic regulators which promoting the progression of GCs, while those with low expression level were regarded as suppressors with the opposite effects 6-11 . Furthermore, regulating expression level of SOX genes in certain cancer cell lines could influence cell proliferation and apoptosis in vitro but without known mechanisms 12,13 .…”