title: Essential roles of epithelial bone morphogenetic protein signaling during prostatic development.
abstract: Prostate is a male sex-accessory organ. The prostatic epithelia consist primarily of basal and luminal cells that differentiate from embryonic urogenital sinus epithelia. Prostate tumors are believed to originate in the basal and luminal cells. However, factors that promote normal epithelial differentiation have not been well elucidated, particularly for bone morphogenetic protein (Bmp) signaling. This study shows that Bmp signaling prominently increases during prostatic differentiation in the luminal epithelia, which is monitored by the expression of phosphorylated Smad1/5/8. To elucidate the mechanism of epithelial differentiation and the function of Bmp signaling during prostatic development, conditional male mutant mouse analysis for the epithelial-specific Bmp receptor 1a (Bmpr1a) was performed. We demonstrate that Bmp signaling is indispensable for luminal cell maturation, which regulates basal cell proliferation. Expression of the prostatic epithelial regulatory gene Nkx3.1 was significantly reduced in the Bmpr1a mutants. These results indicate that Bmp signaling is a key factor for prostatic epithelial differentiation, possibly by controlling the prostatic regulatory gene Nkx3.1.
authors.affiliation: Department of Developmental Genetics (A.O., G.Y.), Institute of Advanced Medicine, Wakayama Medical University, Wakayama, 641-8509, Japan; Okazaki Institute for Integrative Bioscience (S.M., Y.O.), National Institute for Basic Biology, National Institutes of Natural Science, Okazaki, 444-8787, Japan; Department of Clinical Anatomy (M.H.), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, 113-8591, Japan; Department of Oncologic Pathology (K.I.), and Nephro-Urologic Surgery and Andrology (Y.S.), Mie University Graduate School of Medicine, Tsu, Mie, 514-8507, Japan; Department of Animal Bioscience (H.O.), Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga, 526-0829, Japan; and Division of Reproductive Engineering (N.N.), Center for Animal Resources and Development (CARD), Kumamoto University, Kumamoto 860-0811, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Omori
authors.forename: Shinichi
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Ogino
authors.forename: Masayo
authors.initials: M
authors.lastname: Harada
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Ishii
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sugimura
authors.forename: Hajime
authors.initials: H
authors.lastname: Ogino
authors.forename: Naomi
authors.initials: N
authors.lastname: Nakagata
authors.forename: Gen
authors.initials: G
authors.lastname: Yamada
mesh_terms: D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009154:Mutation; D010766:Phosphorylation; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D051785:Smad Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D018398:Homeodomain Proteins; C102837:Nkx3-1 protein, mouse; D011944:Receptors, Androgen; D051785:Smad Proteins; D014157:Transcription Factors; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I
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