Role of estrogen receptor β in colonic epithelium

Osamu Wada-Hiraike, Otabek Imamov, Haruko Hiraike, Kjell Hultenby, Thomas Schwend, Yoko Omoto, Margaret Warner, Jan Åke Gustafsson

Research output: Contribution to journalArticlepeer-review

217 Scopus citations


Several papers report that the colon is one of the tissues regulated by estrogen receptor (ER)β. To better understand the physiological role of ERβ in colonic tissue, we have compared morphology, proliferation, and differentiation of colonic epithelium in ERβ-/- mice and WT littermates. BrdUrd labeling revealed that the number of proliferating cells was higher in ERβ-/- mice and that the migration of labeled cells toward the luminal surface was faster in ERβ-/- mice than in WT littermates. Additionally, in the absence of ERβ, there was a decrease in apoptosis, which was measured by immunohistochemical staining of cleaved caspase-3. The state of differentiation of the colonic epithelial cells was studied by using epithelial markers. In ERβ-/- mice, there was a significant decrease in the expression of the differentiation marker cytokeratin (CK)20 and in the cellular adhesion molecules α-catenin (an adherens junction protein) and plectin (a hemidesmosomal protein). These changes were also evident by electron microscopy as abnormalities in tight junctions and in the number and shape of desmosomes in ERβ-/- mice. These findings suggest a role for ERβ in the organization and architectural maintenance of the colon. Furthermore, our results indicate that the rapidly proliferating cells of the colonic epithelium in ERβ-/- mice are lost by increased shedding and not by increased apoptosis. In this way, hyperproliferative cells that lack ERβ do not form hyperplastic lesions and do not accumulate in the superficial epithelium.

Original languageEnglish (US)
Pages (from-to)2959-2964
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number8
StatePublished - Feb 21 2006


  • Adhesion
  • Cancer
  • Colon
  • Differentiation
  • Proliferation

ASJC Scopus subject areas

  • Genetics
  • General


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