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Transcriptional co-activator TAZ sustains proliferation and tumorigenicity of neuroblastoma by targeting CTGF and PDGF-β.

Wang M, Liu Y, Zou J, Yang R, Xuan F, Wang Y, Gao N, Cui H - Oncotarget (2015)

Bottom Line: Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells.Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells.Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.

ABSTRACT
Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial event in the pathogenesis of neuroblastoma is to promote proliferation of neuroblasts, which is closely related to poor survival. However, mechanisms for regulation of cell proliferation and tumorigenicity in neuroblastoma are not well understood. Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells. Inhibition of endogenous TAZ attenuated cell proliferation, colony formation and tumor development in neuroblastoma SK-N-AS cell, which could be rescued by re-introduction of TAZ into TAZ-knockdown cells. In addition, we found that overexpressing TAZ-mediated induction of CTGF and PDGF-β expression, cell proliferation and colony formation were inhibited by knocking down CTGF and PDGF-β with siRNA in TAZ-overexpressing cell. Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells. Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

No MeSH data available.


Related in: MedlinePlus

TAZ is commonly expressed in neuroblastomas(A, B) Four neuroblastoma cell lines SK-N-AS, BE(2)-C, SK-N-DZ, and SK-N-F1 were harvested and subjected to Western blot and qRT-PCR to detect TAZ expression. (C) Four neuroblastoma cell lines were fixed and immunostained with TAZ monoclonal antibody (red), nuclei were counterstained with DAPI (blue), and evaluated by immunofluorescent microscopy. (D) Quantitative analysis was performed to evaluate the percentage of TAZ-positive cells in four neuroblastoma cells. Data are presented as mean ± S.D. from three independent experiments.
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Figure 2: TAZ is commonly expressed in neuroblastomas(A, B) Four neuroblastoma cell lines SK-N-AS, BE(2)-C, SK-N-DZ, and SK-N-F1 were harvested and subjected to Western blot and qRT-PCR to detect TAZ expression. (C) Four neuroblastoma cell lines were fixed and immunostained with TAZ monoclonal antibody (red), nuclei were counterstained with DAPI (blue), and evaluated by immunofluorescent microscopy. (D) Quantitative analysis was performed to evaluate the percentage of TAZ-positive cells in four neuroblastoma cells. Data are presented as mean ± S.D. from three independent experiments.

Mentions: Since the elevated expression of TAZ has been found in various cancers [20, 21], we next examined TAZ expression in four neuroblastoma cell lines including SK-N-AS, BE(2)-C, SK-N-DZ and SK-N-F1 cells using Western blot and real-time RT-PCR. As shown in Figure 2A and 2B, TAZ was expressed at varying levels of protein and mRNA in all neuroblastoma cell lines. Among the neuroblastoma cell lines, high level of TAZ was detected in SK-N-AS cells, whereas moderate levels of TAZ were observed in SK-N-DZ and SK-N-F1 cells and low level of TAZ was found in BE(2)-C cells. Consistent with these results, immunofluorescent labeling also revealed that the expression of TAZ was found in neuroblastoma cells (Figure 2C). Quantitative analysis indicated that the percentage of TAZ-positive cells was accounted for 72%, 2%, 24% and 29% in SK-N-AS, BE(2)-C, SK-N-DZ and SK-N-F1 cell lines, respectively (Figure 2D). These observation demonstrated that TAZ is indeed expressed in neuroblastoma cells.


Transcriptional co-activator TAZ sustains proliferation and tumorigenicity of neuroblastoma by targeting CTGF and PDGF-β.

Wang M, Liu Y, Zou J, Yang R, Xuan F, Wang Y, Gao N, Cui H - Oncotarget (2015)

TAZ is commonly expressed in neuroblastomas(A, B) Four neuroblastoma cell lines SK-N-AS, BE(2)-C, SK-N-DZ, and SK-N-F1 were harvested and subjected to Western blot and qRT-PCR to detect TAZ expression. (C) Four neuroblastoma cell lines were fixed and immunostained with TAZ monoclonal antibody (red), nuclei were counterstained with DAPI (blue), and evaluated by immunofluorescent microscopy. (D) Quantitative analysis was performed to evaluate the percentage of TAZ-positive cells in four neuroblastoma cells. Data are presented as mean ± S.D. from three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496235&req=5

Figure 2: TAZ is commonly expressed in neuroblastomas(A, B) Four neuroblastoma cell lines SK-N-AS, BE(2)-C, SK-N-DZ, and SK-N-F1 were harvested and subjected to Western blot and qRT-PCR to detect TAZ expression. (C) Four neuroblastoma cell lines were fixed and immunostained with TAZ monoclonal antibody (red), nuclei were counterstained with DAPI (blue), and evaluated by immunofluorescent microscopy. (D) Quantitative analysis was performed to evaluate the percentage of TAZ-positive cells in four neuroblastoma cells. Data are presented as mean ± S.D. from three independent experiments.
Mentions: Since the elevated expression of TAZ has been found in various cancers [20, 21], we next examined TAZ expression in four neuroblastoma cell lines including SK-N-AS, BE(2)-C, SK-N-DZ and SK-N-F1 cells using Western blot and real-time RT-PCR. As shown in Figure 2A and 2B, TAZ was expressed at varying levels of protein and mRNA in all neuroblastoma cell lines. Among the neuroblastoma cell lines, high level of TAZ was detected in SK-N-AS cells, whereas moderate levels of TAZ were observed in SK-N-DZ and SK-N-F1 cells and low level of TAZ was found in BE(2)-C cells. Consistent with these results, immunofluorescent labeling also revealed that the expression of TAZ was found in neuroblastoma cells (Figure 2C). Quantitative analysis indicated that the percentage of TAZ-positive cells was accounted for 72%, 2%, 24% and 29% in SK-N-AS, BE(2)-C, SK-N-DZ and SK-N-F1 cell lines, respectively (Figure 2D). These observation demonstrated that TAZ is indeed expressed in neuroblastoma cells.

Bottom Line: Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells.Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells.Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Silkworm Genome Biology, Southwest University, Chongqing, China.

ABSTRACT
Neuroblastoma is a common childhood malignant tumor originated from the neural crest-derived sympathetic nervous system. A crucial event in the pathogenesis of neuroblastoma is to promote proliferation of neuroblasts, which is closely related to poor survival. However, mechanisms for regulation of cell proliferation and tumorigenicity in neuroblastoma are not well understood. Here, we report that overexpression of TAZ in neuroblastoma BE(2)-C cells causes increases in cell proliferation, self renewal and colony formation, which was restored back to its original levels by knockdown of TAZ in TAZ-overexpression cells. Inhibition of endogenous TAZ attenuated cell proliferation, colony formation and tumor development in neuroblastoma SK-N-AS cell, which could be rescued by re-introduction of TAZ into TAZ-knockdown cells. In addition, we found that overexpressing TAZ-mediated induction of CTGF and PDGF-β expression, cell proliferation and colony formation were inhibited by knocking down CTGF and PDGF-β with siRNA in TAZ-overexpressing cell. Overall, our findings suggested that TAZ plays an essential role in regulating cell proliferation and tumorigenesis in neuroblastoma cells. Thus, TAZ seems to be a novel and promising target for the treatment of neuroblastoma.

No MeSH data available.


Related in: MedlinePlus