title: Transcriptional regulation of PES1 expression by c-Jun in colon cancer.
abstract: Pescadillo is a nucleolar protein that has been suggested to be involved in embryonic development and ribosome biogenesis. Deregulated expression of human pescadillo (PES1) was described in some tumors, but its precise roles in tumorigenesis remains unclear. In this study, we generated three monoclonal antibodies recognizing PES1 with high specificity and sensitivity, with which PES1 expression in human colon cancer was analyzed immunohistochemically. Out of 265 colon cancer tissues, 89 (33.6%) showed positive PES1 expression, which was significantly higher than in non-cancerous tissues (P<0.001). Silencing of PES1 in colon cancer cells resulted in decreased proliferation, reduced growth of xenografts, and cell cycle arrest in G1 phase, indicating PES1 functions as an oncogene. We then explored the mechanism by which PES1 expression is controlled in human colon cancers and demonstrated that c-Jun, but not JunB, JunD, c-Fos, or mutant c-Jun, positively regulated PES1 promoter transcription activity. In addition, we mapped -274/-264 region of PES1 promoter as the c-Jun binding sequence, which was validated by chromatin immunoprecipitation and electrophoretic mobility shift assays. Moreover, we demonstrated a positive correlation between c-Jun and PES1 expression in colon cancer cells and colon cancer tissues. Upstream of c-Jun, it was revealed that c-Jun NH2-terminal kinases (JNK) is essential for controlling PES1 expression. Our study, in the first place, uncovers the oncogenic role of PES1 in colon cancer and elucidates the molecular mechanism directing PES1 expression.
authors.affiliation: Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xie
authors.forename: Qin
authors.initials: Q
authors.lastname: Feng
authors.forename: Yahui
authors.initials: Y
authors.lastname: Su
authors.forename: Bin
authors.initials: B
authors.lastname: Dong
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Meng
authors.forename: Like
authors.initials: L
authors.lastname: Qu
authors.forename: Chengchao
authors.initials: C
authors.lastname: Shou
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D011401:Promoter Regions, Genetic; D011506:Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology*; D034622:RNA Interference; D016601:RNA-Binding Proteins; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000502:physiology*
chemical_list: D017931:DNA Primers; C484463:PES1 protein, human; D011506:Proteins; D016755:Proto-Oncogene Proteins c-jun; D016601:RNA-Binding Proteins