Estrogen stimulates the proliferation of human endometrial cancer cells by stabilizing nucleophosmin/B23 (NPM/B23)

Angel Chao*, Chiao Yun Lin, Chia Lung Tsai, Swei Hsueh, Ying Yu Lin, Cheng Tao Lin, Hung Hsueh Chou, Tzu Hao Wang, Chyong Huey Lai, Hsin Shih Wang

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

21 Scopus citations

Abstract

Unopposed estrogen exposure is an important factor in the tumorigenesis of endometrial cancer. Nucleophosmin/B23 (NPM/B23), a phosphoprotein that has pleiotropic functions in cells, plays an important role in various cancers. However, the regulatory role of NPM/B23 in estrogen signaling in endometrial cancer has not been explored. Here, we report that NPM/B23 was required for estrogen-induced endometrial proliferation, and the increase in NPM/B23 was estrogen receptor α-dependent. Furthermore, estrogen increased NPM/B23 protein levels by repressing its ubiquitination and subsequently stabilizing the protein. The overexpression of the alternate reading frame (ARF) suppressed the estrogen-induced increase in the NPM/B23 protein levels, indicating that ARF inhibited the observed estrogen-mediated NPM/B23 stabilization. Our results suggest that one of the effects of estrogen on endometrial proliferation is the suppression of the NPM/B23-ARF interaction and the subsequent increase in NPM/B23 protein levels. This novel characterization of NPM/B23 in estrogen-mediated cell proliferation may extend our understanding of the tumorigenesis of steroid hormone-related cancers.

Original languageEnglish
Pages (from-to)249-259
Number of pages11
JournalJournal of Molecular Medicine
Volume91
Issue number2
DOIs
StatePublished - 02 2013

Keywords

  • ARF
  • ERα
  • Estrogen
  • NPM/B23

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