Mullerian-Inhibiting Substance Regulates NF-κB Signaling in the Prostate in vitro and in vivo

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 99; no. 1; pp. 239 - 244
• Main Authors: Segev, Dorry L., Hoshiya, Yasunori, Hoshiya, Makiko, Tran, Trinh T., Carey, Jennifer L., Stephen, Antonia E., MacLaughlin, David T., Donahoe, Patricia K., Maheswaran, Shyamala
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08.01.2002; National Acad Sciences; The National Academy of Sciences
• Subjects: Androgens; Animals; Anti-Mullerian Hormone; Apoptosis Regulatory Proteins; Biological Sciences; Blotting, Northern; Blotting, Western; Cell Division; Cell growth; Cell lines; CHO Cells; Cricetinae; DNA; Genes, Dominant; Glycoproteins; Growth Inhibitors - metabolism; Growth Inhibitors - physiology; Human growth; Humans; I^KB^a protein; Immediate-Early Proteins - metabolism; In Situ Hybridization; Male; Membrane Glycoproteins - metabolism; Membrane Proteins; Messenger RNA; Mice; Mice, Inbred C3H; Models, Biological; Muellerian-inhibiting substance; Mullerian-inhibiting substance receptors (type II); Neoplasm Proteins; NF-kappa B - metabolism; Polymerase Chain Reaction; Prostate; Prostate - metabolism; Prostate cancer; Prostate gland; Receptors; Recombinant Proteins - metabolism; Ribonucleases - metabolism; RNA, Messenger - metabolism; Signal Transduction; Testicular Hormones - metabolism; Testicular Hormones - physiology; Time Factors; Tumor Cells, Cultured; Up-Regulation
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.221599298

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.