Genes involved in regulation of stem cell properties: studies on their expression in a small cohort of neuroblastoma patients

Melone, Mariarosa Anna Beatrice; Giulano, Maria; Squillaro, Tiziana; Alessio, Nicola; Casale, Fiorina; Mattioli, Eliseo; Cipollaro, Marilena; Giordano, Antonio; Galderisi, Umberto

doi:10.4161/cbt.8.13.8890

Cited by 27 publications

(31 citation statements)

References 30 publications

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“…Melone et al detected the expression of Oct4 in NB cells and tissue samples, but Sox2 expression was not found (29). Gomez-Mateo et al evaluated the expression and clinical significance of Sox2 in NB using immunohistochemical staining and found that high Sox2 protein levels correlate to aggressive disease, indicating that Sox2 protein levels may be an important prognostic indicator of NB (30).…”

Section: Discussionmentioning

confidence: 99%

Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy

Yang

Zheng

et al. 2012

Oncol Rep

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Abstract. Neuroblastoma (NB) is the most common extracranial solid tumor in childhood and the most frequently diagnosed neoplasm during infancy. Oct4 and Sox2 are essential transcription factors for embryonic development and play key roles in determining the fate of stem cells. In this study, we aimed to investigate the expression of Oct4 and Sox2 in NB tissues, and evaluated their relationship with various clinicopathological parameters. Oct4 and Sox2 expression in 65 samples of NB and paracancerous tissues was examined by real-time PCR. The relationship between Oct4 and Sox2 expression and clinical data was assessed. To detect Oct4 and Sox2 expression at the protein level, western blot analyses and immunohistochemical staining were employed. We found that the expression levels of Oct4 and Sox2 in NB tissues were significantly higher than those in paracancerous tissues (P<0.05). Oct4 and Sox2 expression was significantly correlated to the clinical stage of NB, but not other clinicopathological parameters including patient gender and age, tumor size, location and histological classification. In stage III and IV tumors, Oct4 and Sox2 expression was significantly decreased in the chemotherapy subgroup as compared with that of the non-chemotherapy subgroup (P<0.05). These findings suggest that the expression of Oct4 and Sox2 may correlate with the genesis and progression of NB. In addition, Oct4 and Sox2 expression can be inhibited by chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy

Yang

Zheng

et al. 2012

Oncol Rep

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“…BE(2)-C cells have a typical I-type phenotype, and show consistent morphological and biochemical responses to differentiation-inducing agents (12,23,24). We further established stable cell lines that overexpressed and had downregulated expression of SOX2 by infecting BE(2)-C cells via lentiviral transduction vectors, following which we explored the functions of SOX2 in cell proliferation, clonogenicity, tumorigenicity and differentiation.…”

Section: Introductionmentioning

confidence: 99%

SOX2 promotes tumorigenicity and inhibits the differentiation of I-type neuroblastoma cells

Yang¹,

Zheng²,

Xiao³

et al. 2014

International Journal of Oncology

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Abstract. SOX2 is a transcription factor associated with the pluripotency, proliferative potential, and self-renewing properties observed with embryonic stem cells and germ cells. SOX2 expression has been reported in several cancers and is implicated in tumorigenesis. We previously found that SOX2 expression was correlated to the clinical stage of neuroblastoma. Recently, we found that SOX2 overexpression occurs in I-type neuroblastoma cells (BE(2)-C cells). To elucidate the tumorigenic function of SOX2, we established a SOX2 overexpressed BE(2)-C cell line. SOX2 overexpressed cells showed higher tumorigenicity than control cells and exhibited decreased expression levels of marker proteins of N-or S-type cells after agent-induced differetiation. By contrast, in cells where SOX2 mRNA expression was knocked down by genespecific siRNA, tumorigenicty was significantly decreased and the expression levels of marker proteins of N-or S-type cells were upregulated. In conclusion, our findings indicate an important function for SOX2 in promoting tumorigenicity of I-type neuroblastoma cells and in inhibiting their differentiation, suggesting that SOX2 might be a potential therapeutic target in neuroblastoma.

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“…OCT4 has been used as a cell marker in NB to identify progenitor cells (12)(13)(14)(15)(16)(17). Our study showed that the expression levels of OCT4 strongly correlated with the stemness of NB I-type cells BE (2)-C. High expression of OCT4 increases grades and correlates with tumor progression and malignancy in glioma, a nervous system malignant tumor (8).…”

Section: Discussionmentioning

confidence: 62%

“…Recent findings demonstrated that OCT4 also plays an oncogenic role and is expressed in some cancer stem cells (8)(9)(10)(11). Furthermore, previous studies detected the expression of OCT4 in NB primary samples, metastatic bone marrow aspirates, cell lines, and OCT4 is facilitated to identify NB cancer stem cells as the stemness gene (12)(13)(14)(15)(16)(17). OCT4 is proved to have a potential role in maintaining NB cancer stem cell niche localized in the hypoxic zones of the solid tumors in vivo (12) and is used for identification of tumor-derived endothelial cells as a putative marker (17).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of OCT4 promotes differentiation and inhibits growth of BE (2)-C human neuroblastoma I-type cells

Yang

Zheng

et al. 2013

Oncology Reports

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Abstract. In in vitro continuous culture, N (neuroblastic)-, S (substrate adherent)-and I (intermediate)-type cells were identified in human neuroblastoma (NB), where I-type is recognized as a stem cell type. Octamer-binding protein 4 (OCT4) is a cell marker used to identify the stemness of cells, whose roles in regulating I-type NB cells have yet to be fully elucidated. In the present study, we assessed the differentiation regulation role of OCT4 in BE (2)-C of I-type cells. We demonstrated that downregulation of OCT4 expression in BE (2)-C was associated with reduced cell proliferation and loss of colony formation ability on soft agar, and prompted BE (2)-C cells to differentiate to S-type cells. By contrast, overexpression of OCT4 increased cell proliferation and colony formation ratio, but no obvious differentiation promotion was observed. Furthermore, induced differentiation of BE (2)-C cells to S-type by 5-bromo-2'-deoxyuridine (BrdUrd) was accompanied by reduced expression of OCT4.

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Genes involved in regulation of stem cell properties: studies on their expression in a small cohort of neuroblastoma patients

Cited by 27 publications

References 30 publications

Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy

Oct4 and Sox2 are overexpressed in human neuroblastoma and inhibited by chemotherapy

SOX2 promotes tumorigenicity and inhibits the differentiation of I-type neuroblastoma cells

Downregulation of OCT4 promotes differentiation and inhibits growth of BE (2)-C human neuroblastoma I-type cells

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