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EZH2 deletion does not affect acinar regeneration but restricts progression to pancreatic cancer in mice.

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JCI insight 📖 저널 OA 98.1% 2024: 6/6 OA 2025: 19/20 OA 2026: 25/25 OA 2024~2026 2024 Vol.10(3)
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유사 논문
P · Population 대상 환자/모집단
환자: PDAC is correlated to poor prognosis, suggesting a context-dependant effect for EZH2 in PDAC progression
I · Intervention 중재 / 시술
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C · Comparison 대조 / 비교
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O · Outcome 결과 / 결론
we showed that loss of EZH2 activity did not prevent acinar cell regeneration in the absence of oncogenic KRAS (KRASG12D) nor did it increase PanIN formation following KRASG12D activation in adult mice.

Jaune-Pons E, Wang X, Mousavi F, Klassen Z, El Kaoutari A, Berger K

📝 환자 설명용 한 줄

Enhancer of zeste homologue 2 (EZH2) is part of the Polycomb Repressor Complex 2, which promotes trimethylation of lysine 27 on histone 3 (H3K27me3) and gene repression.

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↓ .bib ↓ .ris
APA Jaune-Pons E, Wang X, et al. (2024). EZH2 deletion does not affect acinar regeneration but restricts progression to pancreatic cancer in mice.. JCI insight, 10(3). https://doi.org/10.1172/jci.insight.173746
MLA Jaune-Pons E, et al.. "EZH2 deletion does not affect acinar regeneration but restricts progression to pancreatic cancer in mice.." JCI insight, vol. 10, no. 3, 2024.
PMID 39739419 ↗

Abstract

Enhancer of zeste homologue 2 (EZH2) is part of the Polycomb Repressor Complex 2, which promotes trimethylation of lysine 27 on histone 3 (H3K27me3) and gene repression. EZH2 is overexpressed in many cancers, and studies in mice attributed both prooncogenic and tumor suppressive functions to EZH2 in pancreatic ductal adenocarcinoma (PDAC). EZH2 deletion enhances de novo KRAS-driven neoplasia following pancreatic injury, while increased EZH2 expression in patients with PDAC is correlated to poor prognosis, suggesting a context-dependant effect for EZH2 in PDAC progression. In this study, we examined EZH2 in pre- and early neoplastic stages of PDAC. Using an inducible model to delete the SET domain of EZH2 in adult acinar cells (EZH2ΔSET), we showed that loss of EZH2 activity did not prevent acinar cell regeneration in the absence of oncogenic KRAS (KRASG12D) nor did it increase PanIN formation following KRASG12D activation in adult mice. Loss of EZH2 did reduce recruitment of inflammatory cells and, when combined with a more aggressive PDAC model, promoted widespread PDAC progression and remodeling of the tumor microenvironment. This study suggests that expression of EZH2 in adult acinar cells restricts PDAC initiation and progression by affecting both the tumor microenvironment and acinar cell differentiation.

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