Consideration of GREB1 as a potential therapeutic target for hormone-responsive or endocrine-resistant cancers

Hodgkinson, Kendra; Vanderhyden, Barbara C.

doi:10.1517/14728222.2014.936382

Cited by 19 publications

(20 citation statements)

References 45 publications

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“…2a). Notably, expression of GREB1 is a predictive biomarker for breast cancer endocrine resistance 22,23 and low expression of GREB1 is associated with reduced relapsefree survival in 742 patients with ER+ breast cancer treated with endocrine therapy 24 (logrank P = 0.0056) ( Fig. 1g).…”

Section: Resultsmentioning

confidence: 99%

Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer

et al. 2020

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Endocrine therapy resistance frequently develops in estrogen receptor positive (ER+) breast cancer, but the underlying molecular mechanisms are largely unknown. Here, we show that 3-dimensional (3D) chromatin interactions both within and between topologically associating domains (TADs) frequently change in ER+ endocrine-resistant breast cancer cells and that the differential interactions are enriched for resistance-associated genetic variants at CTCFbound anchors. Ectopic chromatin interactions are preferentially enriched at active enhancers and promoters and ER binding sites, and are associated with altered expression of ERregulated genes, consistent with dynamic remodelling of ER pathways accompanying the development of endocrine resistance. We observe that loss of 3D chromatin interactions often occurs coincidently with hypermethylation and loss of ER binding. Alterations in active A and inactive B chromosomal compartments are also associated with decreased ER binding and atypical interactions and gene expression. Together, our results suggest that 3D epigenome remodelling is a key mechanism underlying endocrine resistance in ER+ breast cancer.

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Section: Resultsmentioning

confidence: 99%

Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer

et al. 2020

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“…Another downregulated protein is the growth regulation by estrogen in breast cancer 1 (GREB1). This protein is over expressed in ER + untreated (MCF-7) and can be associated with the signaling pathway of estrogen growth factor receptor that regulates cancer growth and proliferation, thus this protein at a great potential to be considered as a therapeutic target for breast cancer ( 65 , 66 ).…”

Section: Resultsmentioning

confidence: 99%

“…This protein was found to be a potential therapeutic target in cancer treatment ( 45 , 46 , 63 , 64 ). GREB1 a protein which is originally upregulated in ER + breast cancers such as MCF-7 cells and results in upregulation of ER survival signaling through the growth factor ligand, resulting in increased growth and proliferation ( 45 , 46 , 65 , 66 ). Metformin treatment reduced GREB1’s expression, which might result with a negative progression of the disease, therefore GREB1 protein can be considered as another target of cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Screening Novel Molecular Targets of Metformin in Breast Cancer by Proteomic Approach

Al-Zaidan

Ruz

Malki

2017

Front. Public Health

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Metformin is a commonly prescribed antihyperglycemic drug, and has been investigated in vivo and in vitro for its effect to improve the comorbidity of diabetes and various types of cancers. Several studies investigated the therapeutic mechanisms of metformin on cancer cells, but the exact mechanism of metformin’s effect on the proteomic pathways of cancer cells is yet to be further investigated. The main objective of our research line is to discover safe and alternative therapeutic options for breast cancer, we aimed in this study to design a novel “bottom up proteomics workflow” in which proteins were first broken into peptides to reveal their identity, then the proteomes were precisely evaluated using spectrometry analysis. In our study, metformin suppressed cell proliferation and induced apoptosis in human breast carcinoma cell line MCF-7 with minimal toxicity to normal breast epithelial cells MCF-10. Metformin induced apoptosis by arresting cells in G1 phase as evaluated by flow cytometric analysis. Moreover, The G1 phase arrest for the MCF-7 has been confirmed by increased expression levels of p21 and reduction in cyclin D1 level. Additionally, metformin increased the expression levels of p53, Bax, Bad while it reduced expression levels of Akt, Bcl-2, and Mdm2. The study employed a serviceable strategy that investigates metformin-dependent changes in the proteome using a literature-derived network. The protein extracts of the treated and untreated cell lines were analyzed employing proteomic approaches; the findings conveyed a proposed mechanism of the effectual tactics of metformin on breast cancer cells. Metformin proposed an antibreast cancer effect through the examination of the proteomic pathways upon the MCF-7 and MCF-10A exposure to the drug. Our findings proposed prolific proteomic changes that revealed the therapeutic mechanisms of metformin on breast cancer cells upon their exposure. In conclusion, the reported proteomic pathways lead to increase the understanding of breast cancer prognosis and permit future studies to examine the effect of metformin on the proteomic pathways against other types of cancers. Finally, it suggests the possibility to develop further therapeutic generations of metformin with increased anticancer effect through targeting specific proteomes.

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“…16 Although its exact function in the cascade of hormone action remains unclear, GREB1 may regulate proliferation in hormone responsive ovarian and endometrial cancer cells and thus be a candidate for further consideration as a potential therapeutic target. 17 NCOA2, which maps to chromosomal band 8q13, is a member of the p160 steroid receptor coactivator gene family. 18 NCOA2 is well known for its involvement in chimeric transcripts in hematologic malignancies and soft tissue tumors.…”

Section: Discussionmentioning

confidence: 99%

RNA‐sequencing identifies novel GREB1‐NCOA2 fusion gene in a uterine sarcoma with the chromosomal translocation t(2;8)(p25;q13)

Brunetti

Panagopoulos

Gorunova

et al. 2017

Genes Chromosomes & Cancer

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Sarcomas account for 3% of all uterine malignancies and many of them are characterized by acquired, specific fusion genes whose detection has increased pathogenetic knowledge and diagnostic precision. We describe a novel fusion gene, GREB1‐NCOA2, detected by transcriptome sequencing and validated by reverse transcriptase polymerase chain reaction and Sanger sequencing in an undifferentiated uterine sarcoma. The chimeric transcript was an in‐frame fusion between exon 3 of GREB1 and exon 15 of NCOA2. The fusion is reported here for the first time, but it involves the GREB1 gene, an important promoter of tumor growth and progression, and NCOA2 which is known to be involved in transcriptional regulation. The alteration and recombination of these genes played a role in the tumorigenesis and/or progression of this sarcoma.

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Consideration of GREB1 as a potential therapeutic target for hormone-responsive or endocrine-resistant cancers

Cited by 19 publications

References 45 publications

Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer

Epigenetic reprogramming at estrogen-receptor binding sites alters 3D chromatin landscape in endocrine-resistant breast cancer

Screening Novel Molecular Targets of Metformin in Breast Cancer by Proteomic Approach

RNA‐sequencing identifies novel GREB1‐NCOA2 fusion gene in a uterine sarcoma with the chromosomal translocation t(2;8)(p25;q13)

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