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Intestinal estrogen...
Intestinal estrogen receptor beta suppresses colon inflammation andtumorigenesis in both sexes
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- Hases, Linnea (author)
- Karolinska Institutet,KTH,Cellulär och klinisk proteomik,Experimental Oncology
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- Indukuri, Rajitha (author)
- Karolinska Institutet,KTH,Cellulär och klinisk proteomik
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- Birgersson, Madeleine (author)
- Karolinska Institutet
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Nguyen-Vu, Trang (author)
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- Lozano, Rodrigo (author)
- Karolinska Institutet
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Saxena, Ashish (author)
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- Hartman, Johan (author)
- Karolinska Institutet
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Frasor, Jonna (author)
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- Gustafsson, Jan-Åke (author)
- Karolinska Institutet
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- Katajisto, Pekka (author)
- Karolinska Institutet
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- Archer, Amena (author)
- Karolinska Institutet,KTH,Skolan för kemi, bioteknologi och hälsa (CBH)
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- Williams, Cecilia, Professor, 1969- (author)
- Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap
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(creator_code:org_t)
- Elsevier BV, 2020
- 2020
- English.
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In: Cancer Letters. - : Elsevier BV. - 0304-3835 .- 1872-7980. ; 492, s. 54-62
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https://doi.org/10.1...
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https://kth.diva-por... (primary) (Raw object)
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Abstract
Subject headings
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- Estrogen hormones protect against colorectal cancer (CRC) and a preventative role of estrogen receptor beta (ERβ) on CRC has been supported using full knockout animals. However, it is unclear through which cells or organ ERβ mediates this effect. To investigate the functional role of intestinal ERβ during colitis-associated CRC we used intestine-specific ERβ knockout mice treated with azoxymethane and dextran sodium sulfate, followed by ex vivo organoid culture to corroborate intrinsic effects. We explored genome-wide impact on TNFα signaling using human CRC cell lines and chromatin immunoprecipitation assay to mechanistically characterize the regulation of ERβ. Increased tumor formation in males and tumor size in females was noted upon intestine-specific ERβ knockout, accompanied by enhanced local expression of TNFα, deregulation of key NFκB targets, and increased colon ulceration. Unexpectedly, we noted especially strong effects in males. We corroborated that intestinal ERβ protects against TNFα-induced damage intrinsically, and characterized an underlying genome-wide signaling mechanism in CRC cell lines whereby ERβ binds to cis-regulatory chromatin areas of key NFκB regulators. Our results support a protective role of intestinal ERβ against colitis-associated CRC, proposing new therapeutic strategies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- AOM/DSS
- CRC
- Colitis
- NFκB
- TNFα
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
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Hases, Linnea
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Indukuri, Rajith ...
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Birgersson, Made ...
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Nguyen-Vu, Trang
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Lozano, Rodrigo
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Saxena, Ashish
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show more...
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Hartman, Johan
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Frasor, Jonna
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Gustafsson, Jan- ...
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Katajisto, Pekka
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Archer, Amena
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Williams, Cecili ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
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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 Cancer and Oncol ...
- Articles in the publication
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Cancer Letters
- By the university
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Royal Institute of Technology
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Karolinska Institutet