SOX2 promotes tumorigenesis and increases the anti-apoptotic property of human prostate cancer cell

Abstract

SRY-related HMG-box gene 2 (SOX2) is one of the key regulatory genes that maintain the pluripotency and self-renewal properties in embryonic stem cells. Here we used immunohistochemistry to analyze the expression of SOX2 in human prostate tissues and found it contributed to tumorigenesis and correlated with histologic grade and Gleason score. We further investigated SOX2's function in cell growth and apoptosis process by using a human prostate cancer cell line DU145 with SOX2 overexpression or down-regulation. Cell cycle assay revealed that SOX2 promoted cell growth and increased the percentage of cells in S phase. In vitro and in vivo xenograft experiments in NOD/SCID mice further demonstrated that SOX2 increased the apoptosis-resistant properties of DU145 cells with decreased function of store-operated Ca(2+) entry and reduced expression of Orai1 at both mRNA and protein levels, suggesting a potential mechanism that contributes to the anti-apoptotic property of SOX2. To our knowledge, this study is the first to investigate SOX2's function in tumorigenesis and apoptosis of human prostate cancer and to elucidate its regulatory effect on the activity of store-operated Ca(2+) channels. Our results support the concept that SOX2 has the potential to be a significant marker to evaluate the progression of prostate cancer and serve as a potentially useful target for prostate cancer therapy.

Gene expression signatures for identifying diffuse-type gastric cancer associated with epithelial-mesenchymal transition

“…Furthermore, 94 probe sets were extracted that were upregulated in diffuse-type GC compared with intestinal-type GC on the U95Av2 platform. (20)(21)(22). NOTCH1, which plays a well-known role in cancer development and EMT, was also upregulated in diffuse-type GC compared with MSCs.…”

Repeated ovarian stimulation does not affect the expression level of proteins involved in cell cycle control in mouse ovaries and fallopian tubes

“…By contrast, in the FT, cyclin D1 Oct3/4 is a transcription factor which plays important roles in ES cells and, together with Sox-2, acts as potent regulators of cell differentiation, especially during peri-implantation development [28] and during ESC differentiation [29]. In addition, the transcription factor Sox-2 regulates the complex transcriptional network that maintains the unique characteristics of embryonic stem cells [30] and the anti-apoptosis property of human cancer stem cells [31]. Literature data show that expression of both these transcription factors is modified in an expanding list of cancers [32,33].…”

Kanserde yeni bir hedef haline gelen çok yönlü Sox2 geni

“…Sox2, insan prostat DU145 kanser hücrelerinde tümör oluşumunu destekleyip, apoptozisten kurtulmayı sağlamıştır. Prostat kanserinin ilerlemesinde artmış Sox2 ifadesinin bir biyo-belirteç olabileceği ve bu kanserin tedavisinde moleküler hedef olabileceği belirlenmiştir (68). EGFR mutasyonlu NSCLC TKI dirençli tümörlerde Sox2'i inhibe etmek için PI3K/Akt inhibitörlerinin kullanılmasının yararlı olabileceği düşünülmektedir (69).…”

“…EGFR mutasyonlu NSCLC TKI dirençli tümörlerde Sox2'i inhibe etmek için PI3K/Akt inhibitörlerinin kullanılmasının yararlı olabileceği düşünülmektedir (69). Bazı farklılıklar olsa da Sox2'nin farklı tümör modellerinde kanser hücrelerinin antiapoptotik özelliğinin oluşmasına katkı sağladığı açıklanmıştır (38,59,68).…”