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

Cancer Sci. 2017 Apr;108(4):632-640. doi: 10.1111/cas.13196. Epub 2017 Apr 19.

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.

Keywords: Biomarker; cell cycle; endometrial cancer; p21; sex-determining region Y-box 2.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Blotting, Western
  • Cell Line, Tumor
  • Cyclin-Dependent Kinase Inhibitor p21 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Endometrial Neoplasms / diagnosis
  • Endometrial Neoplasms / genetics*
  • Endometrial Neoplasms / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Middle Aged
  • Prognosis
  • RNA Interference
  • Reverse Transcriptase Polymerase Chain Reaction
  • SOXB1 Transcription Factors / genetics*
  • SOXB1 Transcription Factors / metabolism
  • Transplantation, Heterologous
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p21
  • SOX2 protein, human
  • SOXB1 Transcription Factors
  • TP53 protein, human
  • Tumor Suppressor Protein p53