High expression of p300 in HCC predicts shortened overall survival in association with enhanced epithelial mesenchymal transition of HCC cells

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• 作者：Chihiro Yokomizo^a ; Kanji Yamaguchi^a ; Yoshito Itoh^a ; ^{yitoh@koto.kpu-m.ac.jp"" rel=""nofollow} ; Takeshi Nishimura^a ; Atsushi Umemura^a ; Masahito Minami^a ; Kohichiroh Yasui^a ; Hironori Mitsuyoshi^a ; Hideki Fujii^a ; Nozomi Tochiki^a ; Tomoki Nakajima^b ; Takeshi Okanoue^c ; Toshikazu Yoshikawa^a
• 关键词：P300 ; HCC ; Overall survival ; E-cadherin ; Tumor invasion
• 刊名：Cancer Letters
• 出版年：2011
• 出版时间：28 November 2011
• 年：2011
• 卷：310
• 期：2
• 页码：140-147
• 全文大小：810 K

文摘

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.