title: Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset.
abstract: Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets.
authors: Laboratory of Genomics and Molecular Biology, CIPE-AC Camargo Hospital, São Paulo, SP, Brasil.
authors: M
authors: M
authors: Maschietto
authors: A P
authors: AP
authors: Trapé
authors: F S
authors: FS
authors: Piccoli
authors: T I
authors: TI
authors: Ricca
authors: A A M
authors: AA
authors: Dias
authors: R A
authors: RA
authors: Coudry
authors: P A
authors: PA
authors: Galante
authors: C
authors: C
authors: Torres
authors: L
authors: L
authors: Fahhan
authors: S
authors: S
authors: Lourenço
authors: P E
authors: PE
authors: Grundy
authors: B
authors: B
authors: de Camargo
authors: S
authors: S
authors: de Souza
authors: E J
authors: EJ
authors: Neves
authors: F A
authors: FA
authors: Soares
authors: H
authors: H
authors: Brentani
authors: D M
authors: DM
authors: Carraro
mesh_terms: D000818:Animals; D018076:DNA, Complementary / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016162:Genes, Wilms Tumor; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D009693:Nucleic Acid Hybridization; D015398:Signal Transduction; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology; D051153:Wnt Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D018076:DNA, Complementary; C435831:WNT5B protein, human; D051153:Wnt Proteins