Limits...
Essential role of GATA3 in regulation of differentiation and cell proliferation in SK-N-SH neuroblastoma cells.

Peng H, Ke XX, Hu R, Yang L, Cui H, Wei Y - Mol Med Rep (2014)

Bottom Line: Neuroblastoma is a common solid malignant tumor of the sympathetic nervous system, which contributes to 15% of cancer‑related mortality in children.The results demonstrated that GATA3 is a prognostic marker for survival in patients with neuroblastoma, and that high‑level GATA3 expression is associated with increased self‑renewal and proliferation of neuroblastoma cells.Retinoic acid treatment led to GATA3 downregulation together with neuronal differentiation, suppression of cell proliferation and inhibition of tumorigenecity in neuroblastoma cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

ABSTRACT
Neuroblastoma is a common solid malignant tumor of the sympathetic nervous system, which contributes to 15% of cancer‑related mortality in children. The differentiation status of neuroblastoma is correlated with clinical outcome, and the induction of differentiation thus constitutes a therapeutic approach in this disease. However, the molecular mechanisms that control the differentiation of neuroblastoma remain poorly understood. The present study aimed to define whether GATA3 is involved in the differentiation of neuroblastoma cells. The results demonstrated that GATA3 is a prognostic marker for survival in patients with neuroblastoma, and that high‑level GATA3 expression is associated with increased self‑renewal and proliferation of neuroblastoma cells. Retinoic acid treatment led to GATA3 downregulation together with neuronal differentiation, suppression of cell proliferation and inhibition of tumorigenecity in neuroblastoma cells. These findings suggest that GATA3 is a key regulator of neuroblastoma differentiation, and provide a novel potential therapeutic strategy for the induction of neuroblastoma differentiation.

Show MeSH

Related in: MedlinePlus

Effect of GATA3 overexpression on the tumorigenicity of neuroblastoma cells. (A) Western blot analysis of GATA3 and peripherin expression in SK-N-SH cells treated with RA or DMSO. (B) Western blot analysis of GATA3 and Mash1 expression in SK-N-SH cells with GFP or GATA3 overexpression. α-tubulin levels were used as a loading control. (C) Tumor growth in NOD/SCID mice injected with indicated SK-N-SH cells. (D) Scatter plot of xenograft tumor weight with horizontal lines indicating the mean per group. (E) Xenograft tumor volume was measured using calipers. *P≤0.05. Scale bar=5 cm. GFP, green fluorescent protein; Un, untreated; RA-3D/RA-7D, three and seven days, respectively, following retinoic acid administration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4262502&req=5

f5-mmr-11-02-0881: Effect of GATA3 overexpression on the tumorigenicity of neuroblastoma cells. (A) Western blot analysis of GATA3 and peripherin expression in SK-N-SH cells treated with RA or DMSO. (B) Western blot analysis of GATA3 and Mash1 expression in SK-N-SH cells with GFP or GATA3 overexpression. α-tubulin levels were used as a loading control. (C) Tumor growth in NOD/SCID mice injected with indicated SK-N-SH cells. (D) Scatter plot of xenograft tumor weight with horizontal lines indicating the mean per group. (E) Xenograft tumor volume was measured using calipers. *P≤0.05. Scale bar=5 cm. GFP, green fluorescent protein; Un, untreated; RA-3D/RA-7D, three and seven days, respectively, following retinoic acid administration.

Mentions: Furthermore, the RA-induced neuroblastoma differentiation was accompanied by GATA3 downregulation and the upregulation of peripherin, a neuronal differentiation marker (35) (Fig. 5A). GATA3 upregulation led to a significant increase in the expression of Mash1 (Fig. 5B), which is a potential stem cell or progenitor cell marker (36,37). Similar results were obtained from the in vivo tumorigenicity analysis using the SK-N-SH neuroblastoma cells. Overexpression of GATA3 in SK-N-SH cells significantly enhanced tumor growth and development in NOD/SCID mice (Fig. 5C–E). These data indicate that GATA3 is not only a prognostic marker, but also an important mediator of cell proliferation and differentiation.


Essential role of GATA3 in regulation of differentiation and cell proliferation in SK-N-SH neuroblastoma cells.

Peng H, Ke XX, Hu R, Yang L, Cui H, Wei Y - Mol Med Rep (2014)

Effect of GATA3 overexpression on the tumorigenicity of neuroblastoma cells. (A) Western blot analysis of GATA3 and peripherin expression in SK-N-SH cells treated with RA or DMSO. (B) Western blot analysis of GATA3 and Mash1 expression in SK-N-SH cells with GFP or GATA3 overexpression. α-tubulin levels were used as a loading control. (C) Tumor growth in NOD/SCID mice injected with indicated SK-N-SH cells. (D) Scatter plot of xenograft tumor weight with horizontal lines indicating the mean per group. (E) Xenograft tumor volume was measured using calipers. *P≤0.05. Scale bar=5 cm. GFP, green fluorescent protein; Un, untreated; RA-3D/RA-7D, three and seven days, respectively, following retinoic acid administration.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262502&req=5

f5-mmr-11-02-0881: Effect of GATA3 overexpression on the tumorigenicity of neuroblastoma cells. (A) Western blot analysis of GATA3 and peripherin expression in SK-N-SH cells treated with RA or DMSO. (B) Western blot analysis of GATA3 and Mash1 expression in SK-N-SH cells with GFP or GATA3 overexpression. α-tubulin levels were used as a loading control. (C) Tumor growth in NOD/SCID mice injected with indicated SK-N-SH cells. (D) Scatter plot of xenograft tumor weight with horizontal lines indicating the mean per group. (E) Xenograft tumor volume was measured using calipers. *P≤0.05. Scale bar=5 cm. GFP, green fluorescent protein; Un, untreated; RA-3D/RA-7D, three and seven days, respectively, following retinoic acid administration.
Mentions: Furthermore, the RA-induced neuroblastoma differentiation was accompanied by GATA3 downregulation and the upregulation of peripherin, a neuronal differentiation marker (35) (Fig. 5A). GATA3 upregulation led to a significant increase in the expression of Mash1 (Fig. 5B), which is a potential stem cell or progenitor cell marker (36,37). Similar results were obtained from the in vivo tumorigenicity analysis using the SK-N-SH neuroblastoma cells. Overexpression of GATA3 in SK-N-SH cells significantly enhanced tumor growth and development in NOD/SCID mice (Fig. 5C–E). These data indicate that GATA3 is not only a prognostic marker, but also an important mediator of cell proliferation and differentiation.

Bottom Line: Neuroblastoma is a common solid malignant tumor of the sympathetic nervous system, which contributes to 15% of cancer‑related mortality in children.The results demonstrated that GATA3 is a prognostic marker for survival in patients with neuroblastoma, and that high‑level GATA3 expression is associated with increased self‑renewal and proliferation of neuroblastoma cells.Retinoic acid treatment led to GATA3 downregulation together with neuronal differentiation, suppression of cell proliferation and inhibition of tumorigenecity in neuroblastoma cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Cancer Biotherapy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China.

ABSTRACT
Neuroblastoma is a common solid malignant tumor of the sympathetic nervous system, which contributes to 15% of cancer‑related mortality in children. The differentiation status of neuroblastoma is correlated with clinical outcome, and the induction of differentiation thus constitutes a therapeutic approach in this disease. However, the molecular mechanisms that control the differentiation of neuroblastoma remain poorly understood. The present study aimed to define whether GATA3 is involved in the differentiation of neuroblastoma cells. The results demonstrated that GATA3 is a prognostic marker for survival in patients with neuroblastoma, and that high‑level GATA3 expression is associated with increased self‑renewal and proliferation of neuroblastoma cells. Retinoic acid treatment led to GATA3 downregulation together with neuronal differentiation, suppression of cell proliferation and inhibition of tumorigenecity in neuroblastoma cells. These findings suggest that GATA3 is a key regulator of neuroblastoma differentiation, and provide a novel potential therapeutic strategy for the induction of neuroblastoma differentiation.

Show MeSH
Related in: MedlinePlus