title: Downregulation of WDR20 due to loss of 14q is involved in the malignant transformation of clear cell renal cell carcinoma.
abstract: Previously, we reported that genomic loss of 14q occurs more frequently in high-grade than in low-grade clear cell renal cell carcinomas (ccRCCs), and has a significant impact on the levels of expression of genes located in this region, suggesting that such genes may be involved in the malignant transformation of ccRCCs. Here, we found that six of the genes located in the minimal common region of 14q loss were significantly downregulated in high-grade ccRCCs due to copy number loss. Using a dataset from The Cancer Genome Atlas Research Network, we found that downregulation of one of these six genes, WDR20, was significantly associated with poorer outcome in patients with ccRCC, suggesting that WDR20 downregulation may be involved in the malignant transformation of ccRCCs. In functional assays, exogenous WDR20 significantly inhibited the growth of RCC cell lines and induced apoptosis. Interestingly, the phosphorylation levels of ERK and protein kinase B/AKT, which reportedly contribute to the malignant phenotype of RCC cells, were clearly reduced by exogenous expression of WDR20. Thus, our data suggest that downregulation of WDR20 due to 14q loss may be involved in the malignant transformation of ccRCCs, in part through activation of the ERK and protein kinase B/AKT pathways.
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.|Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Takahashi
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Tsukamoto
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.|Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Tomoki
authors.initials: T
authors.lastname: Kai
authors.affiliation: Research Promotion Institute, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Akinori
authors.initials: A
authors.lastname: Tokunaga
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Nakada
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hijiya
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Uchida
authors.affiliation: Department of Diagnostic Pathology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Daa
authors.affiliation: Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Nomura
authors.affiliation: Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Fuminori
authors.initials: F
authors.lastname: Sato
authors.affiliation: Department of Urology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Mimata
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.|Department of Biology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Matsuura
authors.affiliation: Department of Molecular Pathology, Faculty of Medicine, Oita University, Oita, Japan.
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Moriyama
mesh_terms: D017209:Apoptosis / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D051058:Oncogene Protein v-akt / Q000235:genetics
chemical_list: D002352:Carrier Proteins; C549040:WDR20 protein, human; D051058:Oncogene Protein v-akt
keywords: 14q loss; Apoptosis; The Cancer Genome Atlas; WDR20; clear cell renal cell carcinoma