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Clinical significance of Polycomb gene expression in brain tumors.

Crea F, Hurt EM, Farrar WL - Mol. Cancer (2010)

Bottom Line: Polycomb group (PcG) proteins are crucial for neural cancer stem cell (NCSC) self-renewal.In glioblastoma, EZH2 inhibits differentiation, and activates cancer-, cell cycle- and cellular movement-related genes.In keeping with previously published data, our results suggest that EZH2 is both a prognostic factor and a promising therapy target in brain tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Stem Cell Section, Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.

ABSTRACT
Polycomb group (PcG) proteins are crucial for neural cancer stem cell (NCSC) self-renewal. However, the relative expression levels of PcG genes in different subtypes of brain tumors, their prognostic role and their effects on cellular pathways have not been investigated. For this purpose, we queried the Oncomine database and found that 4 PcG genes (EZH2, RBBP7, SUZ12, YY1) are specifically expressed in brain tumors. EZH2 expression increases with tumor grade in adult and pediatric brain tumors, and is a poor prognostic factor. In glioblastoma, EZH2 inhibits differentiation, and activates cancer-, cell cycle- and cellular movement-related genes. In keeping with previously published data, our results suggest that EZH2 is both a prognostic factor and a promising therapy target in brain tumors.

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Mitotic roles of polo-like kinases. EZH2 associated genes (in red) are highly represented in all mitotic pathways involving polo-like kinases. Data obtained through IPA software.
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Figure 3: Mitotic roles of polo-like kinases. EZH2 associated genes (in red) are highly represented in all mitotic pathways involving polo-like kinases. Data obtained through IPA software.

Mentions: In addition, EZH2 may indirectly activate cell cycle progression, tumorigenesis and invasion, as shown in other cancer types [5]. In this regard, the top canonical pathway activated in EZH2-associated genes was "Mitotic roles of Polo-like kinases" (p = 1.83E-11). As shown in Figure 3, several EZH2-associated genes are involved in this pathway, which regulates mitotic entry and DNA damage-activated checkpoints. Interestingly, Polo kinases orchestrate the self-renewal versus differentiation decision in neural progenitors, by regulating the orientation of mitotic spindles [21]. Additional pathways significantly associated with EZH2 expression in glioma were "ATM signaling" (p = 2.2E-6), "G2/M DNA damage checkpoint" (p = 1.0E-5) and "Sonic hedgehog signaling" (p = 1.5E-3). ATM signaling is involved in DNA repair, while Hedgehog pathway is essential for neural SCs [5]. Our results are in agreement with in vitro findings, showing that EZH2 is required for cell cycle control and SC self-renewal [5].


Clinical significance of Polycomb gene expression in brain tumors.

Crea F, Hurt EM, Farrar WL - Mol. Cancer (2010)

Mitotic roles of polo-like kinases. EZH2 associated genes (in red) are highly represented in all mitotic pathways involving polo-like kinases. Data obtained through IPA software.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2958980&req=5

Figure 3: Mitotic roles of polo-like kinases. EZH2 associated genes (in red) are highly represented in all mitotic pathways involving polo-like kinases. Data obtained through IPA software.
Mentions: In addition, EZH2 may indirectly activate cell cycle progression, tumorigenesis and invasion, as shown in other cancer types [5]. In this regard, the top canonical pathway activated in EZH2-associated genes was "Mitotic roles of Polo-like kinases" (p = 1.83E-11). As shown in Figure 3, several EZH2-associated genes are involved in this pathway, which regulates mitotic entry and DNA damage-activated checkpoints. Interestingly, Polo kinases orchestrate the self-renewal versus differentiation decision in neural progenitors, by regulating the orientation of mitotic spindles [21]. Additional pathways significantly associated with EZH2 expression in glioma were "ATM signaling" (p = 2.2E-6), "G2/M DNA damage checkpoint" (p = 1.0E-5) and "Sonic hedgehog signaling" (p = 1.5E-3). ATM signaling is involved in DNA repair, while Hedgehog pathway is essential for neural SCs [5]. Our results are in agreement with in vitro findings, showing that EZH2 is required for cell cycle control and SC self-renewal [5].

Bottom Line: Polycomb group (PcG) proteins are crucial for neural cancer stem cell (NCSC) self-renewal.In glioblastoma, EZH2 inhibits differentiation, and activates cancer-, cell cycle- and cellular movement-related genes.In keeping with previously published data, our results suggest that EZH2 is both a prognostic factor and a promising therapy target in brain tumors.

View Article: PubMed Central - HTML - PubMed

Affiliation: Cancer Stem Cell Section, Laboratory of Cancer Prevention, National Cancer Institute at Frederick, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA.

ABSTRACT
Polycomb group (PcG) proteins are crucial for neural cancer stem cell (NCSC) self-renewal. However, the relative expression levels of PcG genes in different subtypes of brain tumors, their prognostic role and their effects on cellular pathways have not been investigated. For this purpose, we queried the Oncomine database and found that 4 PcG genes (EZH2, RBBP7, SUZ12, YY1) are specifically expressed in brain tumors. EZH2 expression increases with tumor grade in adult and pediatric brain tumors, and is a poor prognostic factor. In glioblastoma, EZH2 inhibits differentiation, and activates cancer-, cell cycle- and cellular movement-related genes. In keeping with previously published data, our results suggest that EZH2 is both a prognostic factor and a promising therapy target in brain tumors.

Show MeSH
Related in: MedlinePlus