title: The bone morphogenetic protein antagonist Gremlin is overexpressed in             human malignant mesothelioma.
abstract: Gremlin is a member of the bone morphogenetic protein (BMP) antagonist family             and its antagonistic effect is likely through direct binding to BMP proteins.             As an antagonist of BMP, Gremlin plays a role in regulating organogenesis, body             patterning and tissue differentiation. Recent studies have shown a deregulation             of Gremlin in several types of human cancers. However, the role of Gremlin in             human malignant mesothelioma (MM) is still unknown. In this study, we investigated             the expression of Gremlin in human MM. We found that Gremlin mRNA and protein             were both overexpressed in the majority of primary MM tissue samples that we examined.             We also observed high level expression of the Gremlin gene in 4 of the 6 MM cell             lines. Consistently, we found that the Gremlin promoter activity was significantly             elevated in those MM cell lines expressing the Gremlin gene. On the other hand,             no activity of the Gremlin promoter was detected in the two MM cell lines lacking             Gremlin expression. Moreover, to examine the functional significance of the Gremlin             overexpression in MM, we used shRNA to knock down Gremlin expression in MM cell             lines expressing Gremlin and found that inhibition of Gremlin expression significantly             suppressed proliferation of those MM cells. Taken together, our results suggest             that the BMP antagonist Gremlin is overexpressed in MM and that aberrant activation             of Gremlin may play a critical role in the tumorigenesis of human MM.
authors.affiliation: Department of Pathology, The Chinese PLA General Hospital, Capital Medical University, Beijing, PR China.
authors.forename: Dian-Jun
authors.initials: DJ
authors.lastname: Wang
authors.forename: Xiu-Yi
authors.initials: XY
authors.lastname: Zhi
authors.forename: Shu-Cai
authors.initials: SC
authors.lastname: Zhang
authors.forename: Miao
authors.initials: M
authors.lastname: Jiang
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.forename: Xing-Peng
authors.initials: XP
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Zhao
authors.initials: Z
authors.lastname: Chen
authors.forename: Chang-Li
authors.initials: CL
authors.lastname: Wang
mesh_terms: D001483:Base Sequence; D015153:Blotting, Western; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008654:Mesothelioma / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
chemical_list: D019485:Bone Morphogenetic Proteins; C486399:GREM1 protein, human; D036341:Intercellular Signaling Peptides and Proteins