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Histone acetyltransferase MOF is involved in suppression of endometrial cancer and maintenance of ERα stability.

Abstract
Histone acetyltransferase MOF is involved in active transcription regulation through histone H4K16 acetylation. MOF is downexpressed in a number of human tumors, but biological function of MOF in endometrial cancer has not been fully defined. The estrogen receptor α (ERα) is a transcription factor that regulates estrogen-stimulated cell proliferation in hormone-responsive tumors. However, ERα expression is decreased in grade III ECa samples and high expression of ERα is associated with long disease-free survival in ECa. The molecular mechanism for these observations is still unclear. Here we demonstrate knockdown of MOF promotes ECa cell growth and proliferation in vitro and in vivo. Clinical evidence indicates that expression MOF is decreased and positively correlated with that of ERα in ECa tissues. Furthermore, MOF physically interacts with ERα and modulates ERα stability in ECa cells. In addition, MOF modulates expression of a subset of endogenous genes regulated by ERα. Taken together, our results define MOF as a potential tumor suppressor in ECa participates in maintenance of ERα protein stability and regulation of ERα action.
AuthorsYi Wu, Kai Zeng, Chunyu Wang, Shengli Wang, Hongmiao Sun, Wensu Liu, Xiuxia Wang, Jumin Niu, Shu-Yan Cong, Xin Zhou, Yue Zhao
JournalBiochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 509 Issue 2 Pg. 541-548 (02 05 2019) ISSN: 1090-2104 [Electronic] United States
PMID30598260 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2018 Elsevier Inc. All rights reserved.
Chemical References
  • Estrogen Receptor alpha
  • Histone Acetyltransferases
  • KAT8 protein, human
  • Kat8 protein, mouse
Topics
  • Animals
  • COS Cells
  • Cell Line, Tumor
  • Cell Proliferation
  • Chlorocebus aethiops
  • Endometrial Neoplasms (genetics, metabolism, pathology)
  • Endometrium (metabolism, pathology)
  • Estrogen Receptor alpha (analysis, genetics, metabolism)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Histone Acetyltransferases (analysis, genetics, metabolism)
  • Humans
  • Mice, Inbred NOD
  • Mice, SCID
  • Middle Aged
  • Protein Stability

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