PURPOSE: To elucidate the clinicopathological significance and the role of Jun Activation Domain-Binding Protein 1 (JAB1), Ser10-phosphorylated p27 (p27S10), and total p27 in human hepatocellular carcinoma (HCC) prognosis. METHODS: We evaluated the expression of JAB1 and p27S10 in tissues by immunohistochemical and immunoblot analyses. p27 Ser10 phosphorylation and Ser10 phosphorylation-dependent p27-JAB1 interaction were demonstrated in proliferating Huh7 cells following transfection of pEGFP-p27WT/p27S10A/p27S10D plasmids and pcDNA3.1-p27WT/p27S10A/p27S10D-Myc plasmids. Univariate and multivariate analysis were used to determine their role in HCC prognosis. RESULTS: JAB1 and p27S10 are overexpressed in HCC samples compared with paired normal tissues. There was a strong correlation between JAB1 and p27S10 expression (P < 0.001), and expression of both inversely correlated with total p27 levels (P < 0.001). High JAB1 and p27S10 expression correlated with histological grade, vascular invasion, and serum α-fetoprotein (AFP) level (all P < 0.01). Total p27 expression also correlated with histological tumor grade (P = 0.048) and AFP level (P = 0.015). The p27S10(high)/JAB1(high)/p27(1ow) profile was the most reliable indication of poor prognostic. Ser10 phosphorylation increased and total p27 levels decreased in a time-dependent manner in serum-starved Huh7 cells following addition of serum. Immunoprecipitation analysis revealed that p27 Ser-to-Asp substitution at position 10 (S10D) markedly enhanced the interaction between JAB1 and p27, but replacement of S10A reduced binding. CONCLUSIONS: This study revealed that combined JAB1, p27S10, and total p27 expression may serve as a prognostic marker for HCC.
PURPOSE: To elucidate the clinicopathological significance and the role of Jun Activation Domain-Binding Protein 1 (JAB1), Ser10-phosphorylated p27 (p27S10), and total p27 in humanhepatocellular carcinoma (HCC) prognosis. METHODS: We evaluated the expression of JAB1 and p27S10 in tissues by immunohistochemical and immunoblot analyses. p27Ser10 phosphorylation and Ser10 phosphorylation-dependent p27-JAB1 interaction were demonstrated in proliferating Huh7 cells following transfection of pEGFP-p27WT/p27S10A/p27S10D plasmids and pcDNA3.1-p27WT/p27S10A/p27S10D-Myc plasmids. Univariate and multivariate analysis were used to determine their role in HCC prognosis. RESULTS:JAB1 and p27S10 are overexpressed in HCC samples compared with paired normal tissues. There was a strong correlation between JAB1 and p27S10 expression (P < 0.001), and expression of both inversely correlated with total p27 levels (P < 0.001). High JAB1 and p27S10 expression correlated with histological grade, vascular invasion, and serum α-fetoprotein (AFP) level (all P < 0.01). Total p27 expression also correlated with histological tumor grade (P = 0.048) and AFP level (P = 0.015). The p27S10(high)/JAB1(high)/p27(1ow) profile was the most reliable indication of poor prognostic. Ser10 phosphorylation increased and total p27 levels decreased in a time-dependent manner in serum-starved Huh7 cells following addition of serum. Immunoprecipitation analysis revealed that p27Ser-to-Asp substitution at position 10 (S10D) markedly enhanced the interaction between JAB1 and p27, but replacement of S10A reduced binding. CONCLUSIONS: This study revealed that combined JAB1, p27S10, and total p27 expression may serve as a prognostic marker for HCC.
Authors: You Wang; Yingying Wang; Jingying Xiang; Fang Ji; Yan Deng; Chunhui Tang; Shuyun Yang; Qinghua Xi; Rong Liu; Wen Di Journal: Cancer Lett Date: 2013-09-07 Impact factor: 8.679
Authors: M Shirane; Y Harumiya; N Ishida; A Hirai; C Miyamoto; S Hatakeyama; K Nakayama; M Kitagawa Journal: J Biol Chem Date: 1999-05-14 Impact factor: 5.157
Authors: M Pagano; S W Tam; A M Theodoras; P Beer-Romero; G Del Sal; V Chau; P R Yew; G F Draetta; M Rolfe Journal: Science Date: 1995-08-04 Impact factor: 47.728
Authors: Nikhil I Malgaonkar; Abdulwahab Abuderman; M Y Kharma; S A Al-Maweri; N A Alaizari; Ma Altamimi; S Darwish; Bassel Tarakji Journal: J Clin Diagn Res Date: 2016-07-01