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Estrogen Receptor b...
Estrogen Receptor beta (ESR2) Transcriptome and Chromatin Binding in a Mantle Cell Lymphoma Tumor Model Reveal the Tumor-Suppressing Mechanisms of Estrogens
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- Huang, Dan (author)
- Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden.
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- Huang, Zhiqiang (author)
- Karolinska Institutet
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- Indukuri, Rajitha (author)
- KTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Dept Biosci & Nutr
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- Revanna, Chandrashekar Bangalore (author)
- Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden.
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- Berglund, Mattias (author)
- Karolinska Institutet
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- Guan, Jiyu (author)
- Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden.
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- Yakimchuk, Konstantin (author)
- Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden.
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- Damdimopoulos, Anastasios (author)
- Karolinska Institutet
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- Williams, Cecilia, Professor, 1969- (author)
- Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Cellulär och klinisk proteomik,Karolinska Inst, Dept Biosci & Nut
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- Okret, Sam (author)
- Karolinska Institutet
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Karolinska Institutet Karolinska Inst, Dept Biosci & Nutr, SE-14183 Huddinge, Sweden (creator_code:org_t)
- 2022-06-24
- 2022
- English.
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In: Cancers. - : MDPI. - 2072-6694. ; 14:13, s. 3098-
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https://doi.org/10.3...
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Abstract
Subject headings
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- Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma with one of the highest male-tofemale incidence ratios. The reason for this is not clear, but epidemiological as well as experimental data have suggested a role for estrogens, particularly acting through estrogen receptor beta (ESR2). To study the ESR2 effects on MCL progression, MCL cells sensitive and resistant to the Bruton tyrosine kinase inhibitor ibrutinib were grafted to mice and treated with the ESR2-selective agonist diarylpropionitrile (DPN). The results showed that the DPN treatment of mice grafted with both ibrutinib-sensitive and -resistant MCL tumors resulted in impaired tumor progression. To identify the signaling pathways involved in the impaired tumor progression following ESR2 agonist treatment, the transcriptome and ESR2 binding to target genes were investigated by genome-wide chromatin immunoprecipitation in Granta-519 MCL tumors. DPN-regulated genes were enriched in several biological processes that included cell-cell adhesion, endothelial-mesenchymal transition, nuclear factor-kappaB signaling, vasculogenesis, lymphocyte proliferation, and apoptosis. In addition, downregulation of individual genes, such as SOX11 and MALAT1, that play a role in MCL progression was also observed. Furthermore, the data suggested an interplay between the lymphoma cells and the tumor microenvironment in response to the ESR2 agonist. In conclusion, the results clarify the mechanisms by which estrogens, via ESR2, impair MCL tumor progression and provide a possible explanation for the sex-dependent difference in incidence. Furthermore, targeting ESR2 with a selective agonist may be an additional option when considering the treatment of both ibrutinib-sensitive and -resistant MCL tumors.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Hematologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Hematology (hsv//eng)
Keyword
- mantle cell lymphoma
- estrogens
- estrogen receptor beta
- ESR2
- xenograft
- ibrutinib
- RNA sequencing
- chromatin immunoprecipitation
- tumor microenvironment
- macrophages
Publication and Content Type
- ref (subject category)
- art (subject category)
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Cancers
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- By the author/editor
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Huang, Dan
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Huang, Zhiqiang
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Indukuri, Rajith ...
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Revanna, Chandra ...
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Berglund, Mattia ...
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Guan, Jiyu
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Yakimchuk, Konst ...
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Damdimopoulos, A ...
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Williams, Cecili ...
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Okret, Sam
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Hematology
- Articles in the publication
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Cancers
- By the university
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Royal Institute of Technology
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Karolinska Institutet