RRC ID 45022
Author Omori A, Miyagawa S, Ogino Y, Harada M, Ishii K, Sugimura Y, Ogino H, Nakagata N, Yamada G.
Title Essential roles of epithelial bone morphogenetic protein signaling during prostatic development.
Journal Endocrinology
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.
Volume 155(7)
Pages 2534-44
Published 2014-7-1
DOI 10.1210/en.2013-2054
PMID 24731097
PMC PMC4060178
MeSH Animals Bone Morphogenetic Protein Receptors, Type I / genetics* Bone Morphogenetic Protein Receptors, Type I / metabolism Cell Differentiation / genetics Cell Line, Tumor Cell Proliferation Epithelium / metabolism* Epithelium / pathology Female Fluorescent Antibody Technique Gene Expression Regulation, Developmental Homeodomain Proteins / genetics Homeodomain Proteins / metabolism Humans Hyperplasia Male Mice Mice, Inbred C57BL Mice, Inbred ICR Mice, Knockout Mice, Transgenic Mutation Phosphorylation Prostate / metabolism* Prostate / pathology Receptors, Androgen / genetics Receptors, Androgen / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / genetics* Smad Proteins / metabolism Transcription Factors / genetics Transcription Factors / metabolism
IF 3.934
Times Cited 9
Human and Animal Cells PC-3(RCB2145)