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Nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation.

Nakaguro M, Kiyonari S, Kishida S, Cao D, Murakami-Tonami Y, Ichikawa H, Takeuchi I, Nakamura S, Kadomatsu K - Cancer Sci. (2015)

Bottom Line: High PES1 expression was associated with worse overall and relapse-free survival.This growth inhibition was associated with the expression of NB differentiation markers.These data suggest that PES1 is a marker of NB outcome, that it regulates NB cell proliferation, and is associated with NB differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.

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Induced differentiation attenuated PES1 expression in neuroblastoma cell line. (a) Phase contrast images (top panels) and confocal image of fluorescence immunostaining for β-tubulin (Tuj1) (red, bottom panels) of NB39 cells under normal culture conditions (10% FBS; Diff.(−)) and differentiation conditions (1% FBS + 1 μM all-trans retinoic acid [ATRA]; Diff.(+)). Hoechst 33258 was used to visualize nuclei. Scale bar = 100 μm. (b) Quantitative RT-PCR analysis of differentiation-related gene (RET) and PES1 expressions (n = 4). *P < 0.05 normal culture conditions versus differentiation conditions (Student's t-test).
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fig04: Induced differentiation attenuated PES1 expression in neuroblastoma cell line. (a) Phase contrast images (top panels) and confocal image of fluorescence immunostaining for β-tubulin (Tuj1) (red, bottom panels) of NB39 cells under normal culture conditions (10% FBS; Diff.(−)) and differentiation conditions (1% FBS + 1 μM all-trans retinoic acid [ATRA]; Diff.(+)). Hoechst 33258 was used to visualize nuclei. Scale bar = 100 μm. (b) Quantitative RT-PCR analysis of differentiation-related gene (RET) and PES1 expressions (n = 4). *P < 0.05 normal culture conditions versus differentiation conditions (Student's t-test).

Mentions: We then examined whether the induction of differentiation can change the PES1 expression. Historically, various methods have been used to induce NB differentiation, including serum starvation and treatment with all-trans retinoic acid (ATRA).28–31 A derivative of vitamin A, ATRA is essential for development and differentiation. All-trans retinoic acid-induced differentiation of leukemic cells has been shown to dramatically improve the prognosis of patients with acute promyelocytic leukemia.32 In addition, ATRA can differentiate NB cells. We induced differentiation in NB cell lines with serum reduction (from 10% FBS in original culture to 1%) and ATRA (1 μM). This treatment increased the number and length of the neuritic extensions of NB39 and TNB1 cells (Fig.4a, Fig. S2), and these neurites were positive for Tuj1, a neuronal marker. This differentiation induction was further verified by the increased expression of a differentiation-related gene (Fig.4b, Fig. S2).33 Interestingly, the differentiation induction decreased PES1 expression (Fig.4b, Fig. S2). This result suggests the possibility that ATRA-induced differentiation modulates PES1 expression.


Nucleolar protein PES1 is a marker of neuroblastoma outcome and is associated with neuroblastoma differentiation.

Nakaguro M, Kiyonari S, Kishida S, Cao D, Murakami-Tonami Y, Ichikawa H, Takeuchi I, Nakamura S, Kadomatsu K - Cancer Sci. (2015)

Induced differentiation attenuated PES1 expression in neuroblastoma cell line. (a) Phase contrast images (top panels) and confocal image of fluorescence immunostaining for β-tubulin (Tuj1) (red, bottom panels) of NB39 cells under normal culture conditions (10% FBS; Diff.(−)) and differentiation conditions (1% FBS + 1 μM all-trans retinoic acid [ATRA]; Diff.(+)). Hoechst 33258 was used to visualize nuclei. Scale bar = 100 μm. (b) Quantitative RT-PCR analysis of differentiation-related gene (RET) and PES1 expressions (n = 4). *P < 0.05 normal culture conditions versus differentiation conditions (Student's t-test).
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Related In: Results  -  Collection

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fig04: Induced differentiation attenuated PES1 expression in neuroblastoma cell line. (a) Phase contrast images (top panels) and confocal image of fluorescence immunostaining for β-tubulin (Tuj1) (red, bottom panels) of NB39 cells under normal culture conditions (10% FBS; Diff.(−)) and differentiation conditions (1% FBS + 1 μM all-trans retinoic acid [ATRA]; Diff.(+)). Hoechst 33258 was used to visualize nuclei. Scale bar = 100 μm. (b) Quantitative RT-PCR analysis of differentiation-related gene (RET) and PES1 expressions (n = 4). *P < 0.05 normal culture conditions versus differentiation conditions (Student's t-test).
Mentions: We then examined whether the induction of differentiation can change the PES1 expression. Historically, various methods have been used to induce NB differentiation, including serum starvation and treatment with all-trans retinoic acid (ATRA).28–31 A derivative of vitamin A, ATRA is essential for development and differentiation. All-trans retinoic acid-induced differentiation of leukemic cells has been shown to dramatically improve the prognosis of patients with acute promyelocytic leukemia.32 In addition, ATRA can differentiate NB cells. We induced differentiation in NB cell lines with serum reduction (from 10% FBS in original culture to 1%) and ATRA (1 μM). This treatment increased the number and length of the neuritic extensions of NB39 and TNB1 cells (Fig.4a, Fig. S2), and these neurites were positive for Tuj1, a neuronal marker. This differentiation induction was further verified by the increased expression of a differentiation-related gene (Fig.4b, Fig. S2).33 Interestingly, the differentiation induction decreased PES1 expression (Fig.4b, Fig. S2). This result suggests the possibility that ATRA-induced differentiation modulates PES1 expression.

Bottom Line: High PES1 expression was associated with worse overall and relapse-free survival.This growth inhibition was associated with the expression of NB differentiation markers.These data suggest that PES1 is a marker of NB outcome, that it regulates NB cell proliferation, and is associated with NB differentiation.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.

Show MeSH
Related in: MedlinePlus