Mullerian-Inhibiting Substance Regulates NF-κB Signaling in the Prostate in vitro and in vivo
Mullerian-inhibiting substance (MIS) is a member of the transforming growth factor β superfamily, a class of molecules that regulates growth, differentiation, and apoptosis in many cells. MIS type II receptor in the Mullerian duct is temporally and spatially regulated during development and becomes...
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Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 1; pp. 239 - 244 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
National Academy of Sciences
08.01.2002
National Acad Sciences The National Academy of Sciences |
Subjects | |
Online Access | Get full text |
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Summary: | Mullerian-inhibiting substance (MIS) is a member of the transforming growth factor β superfamily, a class of molecules that regulates growth, differentiation, and apoptosis in many cells. MIS type II receptor in the Mullerian duct is temporally and spatially regulated during development and becomes restricted to the most caudal ends that fuse to form the prostatic utricle. In this article, we have demonstrated MIS type II receptor expression in the normal prostate, human prostate cancer cell lines, and tissue derived from patients with prostate adenocarcinomas. MIS induced NF-κB DNA binding activity and selectively up-regulated the immediate early gene IEX-1S in both androgen-dependent and independent human prostate cancer cells in vitro. Dominant negative IκBα expression ablated both MIS-induced increase of IEX-1S mRNA and inhibition of growth, indicating that activation of NF-κB signaling was required for these processes. Androgen also induced NF-κB DNA binding activity in prostate cancer cells but without induction of IEX-1S mRNA, suggesting that MIS-mediated increase in IEX-1S was independent of androgen-mediated signaling. Administration of MIS to male mice induced IEX-1S mRNA in the prostate in vivo, suggesting that MIS may function as an endogenous hormonal regulator of NF-κB signaling and growth in the prostate gland. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 D.L.S. and Y.H. contributed equally to this work. Contributed by Patricia K. Donahoe To whom reprint requests should be addressed at: Department of Pediatric Surgery, WRN 1024, Massachusetts General Hospital, Boston, MA 02114. E-mail: maheswaran@helix.mgh.harvard.edu. |
ISSN: | 0027-8424 1091-6490 |
DOI: | 10.1073/pnas.221599298 |