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Müllerian Inhibiting Substance Inhibits Breast Cancer Cell Growth through an NFκB-mediated Pathway
- Source :
- Journal of Biological Chemistry. 275:28371-28379
- Publication Year :
- 2000
- Publisher :
- Elsevier BV, 2000.
-
Abstract
- Müllerian inhibiting substance (MIS), a member of the transforming growth factor-beta superfamily, induces regression of the Müllerian 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 G(1) phase of the cell cycle and induction of apoptosis. Treatment of breast cancer cells with MIS activated the NFkappaB pathway and selectively up-regulated the immediate early gene IEX-1S, which, when overexpressed, inhibited breast cancer cell growth. Dominant negative IkappaBalpha expression ablated both MIS-mediated induction of IEX-1S and inhibition of growth, indicating that activation of the NFkappaB signaling pathway was required for these processes. These results identify the NFkappaB-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.
- Subjects :
- Anti-Mullerian Hormone
medicine.medical_specialty
Receptors, Peptide
Receptor expression
Estrogen receptor
Antineoplastic Agents
Breast Neoplasms
Biochemistry
Immediate early protein
Immediate-Early Proteins
Internal medicine
Tumor Cells, Cultured
medicine
Animals
Humans
skin and connective tissue diseases
Molecular Biology
Glycoproteins
Membrane Glycoproteins
biology
NF-kappa B
Membrane Proteins
Cell Biology
Transforming growth factor beta
Cell cycle
Growth Inhibitors
Neoplasm Proteins
Testicular Hormones
IκBα
Endocrinology
Receptors, Estrogen
COS Cells
biology.protein
Cancer research
Female
Signal transduction
Apoptosis Regulatory Proteins
Receptors, Transforming Growth Factor beta
Transforming growth factor
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 275
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....8956fa55683fe53f729da26e9b9ae84a