High protein expression of EZH2 is related to unfavorable outcome to tamoxifen in metastatic breast cancer

Reijm, Esther A.; Timmermans, Annemieke M.; Look, Maxime P.; Gelder, Marion E. Meijer–van; Stobbe, Claudia; Deurzen, Carolien H.M. van; Martens, John W.M.; Sleijfer, Stefan; Foekens, John A.; Berns, P.M.J.J.; Jansen, Maurice P.H.M.

doi:10.1093/annonc/mdu391

Cited by 49 publications

(51 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Being a key member of the Drosophila Polycomb group (PcG), EZH2 plays a crucial role in gene expression regulation, maintenance of cell identity, stem cell renewal and oncogenesis. Recent studies have shown that EZH2 overexpression predicts poor patient prognosis and is a frequent event in various cancers, such as breast cancer [1], malignant prostate cancer [2], and hepatocellular carcinoma [3]. There are reports depicting the expression and oncogenic role of EZH2 in lung tumorigenesis [4,5] and EZH2 has been suggested to modulate several pathophysiological processes by promoting cell proliferation and cell cycle progression [6], accelerating cell infiltration and metastasis [7], and inhibiting apoptosis [8].…”

Section: Introductionmentioning

confidence: 99%

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer

Geng¹,

Li²,

Zhou³

et al. 2015

Cancer Letters

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer

Geng¹,

Li²,

Zhou³

et al. 2015

Cancer Letters

View full text Add to dashboard Cite

“…But, unlike CBX7, EZH2 overexpression was highly linked to the proliferation marker MKI67, suggesting a different role of these two proteins in breast tumorigenesis (37). Numerous studies point on the widespread roles of PRC2 (as well as H3K27 methylation) in developmental and differentiation processes of multicellular organisms, and on their implication in fundamental chromatin mechanisms that underlie stem cell regulatory circuits and cancer progression (38).…”

Section: Discussionmentioning

confidence: 99%

Expression of ANRIL–Polycomb Complexes–CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value

Meseure

Vacher

Alsibai

et al. 2016

Molecular Cancer Research

View full text Add to dashboard Cite

ANRIL, a long noncoding RNA (lncRNA), has recently been reported to have a direct role in recruiting polycomb repressive complexes PRC2 and PRC1 to regulate the expression of the p15/CDKN2B-p16/CDKN2A-p14/ARF gene cluster. Expression analysis of ANRIL, EZH2, SUZ12, EED, JARID2, CBX7, BMI1, p16, p15, and p14/ARF genes was evaluated in a large cohort of invasive breast carcinomas (IBC, n ¼ 456) by qRT-PCR and immunohistochemistry (IHC) was performed on CBX7, EZH2, p14, p15, p16, H3K27me3, and H3K27ac. We observed significant overexpression in IBCs of ANRIL (19.7%) and EZH2 (77.0%) and an underexpression of CBX7 (39.7%). Correlations were identified between these genes, their expression patterns, and several classical clinical and pathologic parameters, molecular subtypes, and patient outcomes, as well as with proliferation, epithelial-mesenchymal transition, and breast cancer stem cell markers. Multivariate analysis revealed that combined EZH2/ CBX7 status is an independent prognostic factor (P ¼ 0.001). In addition, several miRNAs negatively associated with CBX7 underexpression and EZH2 overexpression. These data demonstrate a complex pattern of interactions between lncRNA ANRIL, several miRNAs, PRC2/PRC1 subunits, and p15/CDKN2B-p16/CDKN2A-p14/ARF locus and suggest that their expression should be considered together to evaluate antitumoral drugs, in particular the BET bromodomain inhibitors.Implications: This study suggests that the global pattern of expression rather than expression of individual family members should be taken into account when defining functionality of repressive Polycomb complexes and therapeutic targeting potential.

show abstract

“…This study used previously described FFPE tumor tissues which were incorporated into a TMA (n = 379) 29 . Breast cancer tissues derived from patients who underwent tumor resection (between 1985 and 2000) and were treated with first line tamoxifen for recurrent disease, were included in the study.…”

Section: Methodsmentioning

confidence: 99%

Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer

Marchi

Timmermans

Sieuwerts

et al. 2017

Sci Rep

View full text Add to dashboard Cite

In a previous study, we detected a significant association between phosphoserine aminotransferase 1 (PSAT1) hyper-methylation and mRNA levels to outcome to tamoxifen treatment in recurrent disease. We here aimed to study the association of PSAT1 protein levels to outcome upon tamoxifen treatment and to obtain more insight in its role in tamoxifen resistance. A cohort of ER positive, hormonal therapy naïve primary breast carcinomas was immunohistochemically (IHC) stained for PSAT1. Staining was analyzed for association with patient’s time to progression (TTP) and overall response on first-line tamoxifen for recurrent disease. PSAT1 mRNA levels were also assessed by reverse transcriptase quantitative polymerase chain reaction (RT-qPCR; n = 161) and Affymetrix GeneChip (n = 155). Association of PSAT1 to biological pathways on tamoxifen outcome were assessed by global test. PSAT1 protein and mRNA levels were significantly associated to poor outcome to tamoxifen treatment. When comparing PSAT1 protein and mRNA levels, IHC and RT-qPCR data showed a significant association. Global test results showed that cytokine and JAK-STAT signaling were associated to PSAT1 expression. We hereby report that PSAT1 protein and mRNA levels measured in ER positive primary tumors are associated with poor clinical outcome to tamoxifen.

show abstract

High protein expression of EZH2 is related to unfavorable outcome to tamoxifen in metastatic breast cancer

Cited by 49 publications

References 33 publications

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer

Expression of ANRIL–Polycomb Complexes–CDKN2A/B/ARF Genes in Breast Tumors: Identification of a Two-Gene (EZH2/CBX7) Signature with Independent Prognostic Value

Phosphoserine aminotransferase 1 is associated to poor outcome on tamoxifen therapy in recurrent breast cancer

Contact Info

Product

Resources

About