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  • Hases, LinneaKarolinska Institutet,KTH,Cellulär och klinisk proteomik,Experimental Oncology (author)

Intestinal estrogen receptor beta suppresses colon inflammation andtumorigenesis in both sexes

  • Article/chapterEnglish2020

Publisher, publication year, extent ...

  • Elsevier BV,2020
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-283325
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-283325URI
  • https://doi.org/10.1016/j.canlet.2020.06.021DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:144979908URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20201009
  • 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.

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  • Indukuri, RajithaKarolinska Institutet,KTH,Cellulär och klinisk proteomik(Swepub:kth)u1h2gbg8 (author)
  • Birgersson, MadeleineKarolinska Institutet (author)
  • Nguyen-Vu, Trang (author)
  • Lozano, RodrigoKarolinska Institutet (author)
  • Saxena, Ashish (author)
  • Hartman, JohanKarolinska Institutet (author)
  • Frasor, Jonna (author)
  • Gustafsson, Jan-ÅkeKarolinska Institutet (author)
  • Katajisto, PekkaKarolinska Institutet (author)
  • Archer, AmenaKarolinska Institutet,KTH,Skolan för kemi, bioteknologi och hälsa (CBH)(Swepub:kth)u131bapq (author)
  • Williams, Cecilia,Professor,1969-Karolinska Institutet,KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u1ygqmuy (author)
  • KTHCellulär och klinisk proteomik (creator_code:org_t)

Related titles

  • In:Cancer Letters: Elsevier BV492, s. 54-620304-38351872-7980

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