title: High expression of p300 in HCC predicts shortened overall survival in association with enhanced epithelial mesenchymal transition of HCC cells.
abstract: P300 impacts the transcription of several genes involved in biological behavior of human malignancies including hepatocellular carcinomas (HCC). We found p300 is highly expressed in 47% of surgically resected HCC specimens by immunohistochemistry, which correlated with advanced TNM staging (P = 0.034), vascular invasion (P = 0.036), intrahepatic metastasis (P = 0.001) and shortened overall survival (P = 0.028). In vitro study, knocking down of p300 expression in hepatoma cells recovered E-cadherin expression, inhibited the translocation of beta (β)-catenin into the nuclei, decreased cyclin D1 activity and suppressed the migration/invasion of HCC cells. Furthermore, suppression of p300 led to down-regulation of epithelial-mesenchymal transition (EMT)-related molecules such as Snail, Twist and HIF-1 alpha. These observations suggest that p300 contributes to the EMT-related progression of HCCs.
authors.affiliation: Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Yokomizo
authors.forename: Kanji
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Yoshito
authors.initials: Y
authors.lastname: Itoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishimura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Umemura
authors.forename: Masahito
authors.initials: M
authors.lastname: Minami
authors.forename: Kohichiroh
authors.initials: K
authors.lastname: Yasui
authors.forename: Hironori
authors.initials: H
authors.lastname: Mitsuyoshi
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Nozomi
authors.initials: N
authors.lastname: Tochiki
authors.forename: Tomoki
authors.initials: T
authors.lastname: Nakajima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Okanoue
authors.forename: Toshikazu
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000502:physiology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D054337:Cell Dedifferentiation / Q000502:physiology; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation; D050881:E1A-Associated p300 Protein / Q000096:biosynthesis* / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D015820:Cadherins; D034741:RNA, Small Interfering; D019938:Cyclin D1; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human