Mullerian inhibiting substance inhibits breast cancer cell growth through an NFκB-mediated pathway

Dorry L. Segev, Thanh U. Ha, Trinh T. Tran, Mary Kenneally, Paul Harkin, Mira Jung, David T. MacLaughlin, Patricia K. Donahoe, Shyamala Maheswaran

Research output: Contribution to journalArticle

Abstract

Mullerian inhibiting substance (MIS), a member of the transforming growth factor-β superfamily, induces regression of the Mullerian duct in male embryos. In this report, we demonstrate MIS type II receptor expression in normal breast tissue and in human breast cancer cell lines, breast fibroadenoma, and ductal adenocarcinomas. MIS inhibited the growth of both estrogen receptor (ER)-positive T47D and ER-negative MDA-MB-231 breast cancer cell lines, suggesting a broader range of target tissues for MIS action. Inhibition of growth was manifested by an increase in the fraction of cells in the G1 phase of the cell cycle and induction of apoptosis. Treatment of breast cancer cells with MIS activated the NFκB pathway and selectively up-regulated the immediate early gene IEX-1S, which, when overexpressed, inhibited breast cancer cell growth. Dominant negative IκBα expression ablated both MIS-mediated induction of IEX-1S and inhibition of growth, indicating that activation of the NFκB signaling pathway was required for these processes. These results identify the NFκB-mediated signaling pathway and a target gene for MIS action and suggest a putative role for the MIS ligand and its downstream interactors in the treatment of ER-positive as well as negative breast cancers.

Original languageEnglish (US)
Pages (from-to)28371-28379
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number37
DOIs
StatePublished - Sep 15 2000

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Segev, D. L., Ha, T. U., Tran, T. T., Kenneally, M., Harkin, P., Jung, M., MacLaughlin, D. T., Donahoe, P. K., & Maheswaran, S. (2000). Mullerian inhibiting substance inhibits breast cancer cell growth through an NFκB-mediated pathway. Journal of Biological Chemistry, 275(37), 28371-28379. https://doi.org/10.1074/jbc.M004554200