Correlation between tuberous sclerosis complex 2 and glycogen synthase kinase 3 beta levels, and outcomes of patients with hepatocellular carcinoma treated by hepatectomy

被引:20
作者
Huang, Ka-Te [1 ]
Huang, Yue-Han [2 ]
Li, Peng [1 ]
He, Bin [2 ]
Chen, Zhen-Kun [2 ]
Yu, Xia [1 ]
Chen, Jian-Ou [1 ]
Zhang, Qi-Yu [2 ]
Shi, Hong-Qi [2 ]
Shan, Yun-Feng [2 ]
机构
[1] Wenzhou Med Univ, Dept Pathol, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China
[2] Wenzhou Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China
关键词
expression; glycogen synthase kinase 3; hepatectomy; hepatocellular carcinoma; prognosis; tuberous sclerosis complex 2; BREAST-CANCER; SIGNALING PATHWAY; POOR-PROGNOSIS; MTOR; EXPRESSION; GSK3-BETA; INHIBITION; GROWTH; WNT; KINASE-3-BETA;
D O I
10.1111/hepr.12256
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
AimTuberous sclerosis complex 2 (TSC2), a tumor suppressor, may play an essential role in the regulation of cell growth and cell survival under energy stress conditions. In addition, TSC2 may act in concert with Wnt and energy signals by additional phosphorylation of glycogen synthase kinase 3 (GSK3) to regulate cell growth. The expression levels and function of TSC2 and GSK3 in hepatocellular carcinoma (HCC) remain unclear. MethodsThe protein levels of TSC2 and GSK3 were measured by immunohistochemistry in normal liver (n=20), HCC (n=80) and pericancerous tissues (n=80). The correlations between TSC2, and GSK3 levels, clinicopathological features and patient survival were also analyzed. ResultsThe protein levels of TSC2 and GSK3 in HCC tissues were significantly lower than that in normal liver tissues and pericancerous tissues (P<0.05). Decreased TSC2 and GSK3 expression was found to be significantly correlated with advanced clinicopathological characteristics and poor prognosis. The results also showed that TSC2 protein levels were associated with GSK3 expression in HCC specimens. ConclusionThis is the first demonstration that the decreases in TSC2 and GSK3 levels may be associated with vascular invasion, histological grade and tumor-node-metastasis classification.
引用
收藏
页码:1142 / 1150
页数:9
相关论文
共 36 条
[1]   Tuberous Sclerosis Complex-Associated Angiomyolipomas: Focus on mTOR Inhibition [J].
Budde, Klemens ;
Gaedeke, Jens .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2012, 59 (02) :276-283
[2]   Reduced expression of Kruppel-like factor 17 is related to tumor growth and poor prognosis in lung adenocarcinoma [J].
Cai, Xing-dong ;
Zhou, Yan-bin ;
Huang, Li-xia ;
Zeng, Qing-li ;
Zhang, Long-juan ;
Wang, Qin-qin ;
Li, Shao-li ;
Feng, Jian-qiang ;
Han, An-jia .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2012, 418 (01) :67-73
[3]   Involvement of TSC genes and differential expression of other members of the mTOR signaling pathway in oral squamous cell carcinoma [J].
Chakraborty, Sanjukta ;
Mohiyuddin, S. M. Azeem ;
Gopinath, K. S. ;
Kumar, Arun .
BMC CANCER, 2008, 8 (1)
[4]   SIRT1 Promotes Tumorigenesis and Resistance to Chemotherapy in Hepatocellular Carcinoma and its Expression Predicts Poor Prognosis [J].
Chen, Hsieh-Cheng ;
Jeng, Yung-Ming ;
Yuan, Ray-Hwang ;
Hsu, Hey-Chi ;
Chen, Yu-Ling .
ANNALS OF SURGICAL ONCOLOGY, 2012, 19 (06) :2011-2019
[5]   Antroquinonol displays anticancer potential against human hepatocellular carcinoma cells: A crucial role of AMPK and mTOR pathways [J].
Chiang, Po-Cheng ;
Lin, Ssu-Chia ;
Pan, Shiow-Lin ;
Kuo, Ching-Hua ;
Tsai, I-Lin ;
Kuo, Mao-Tien ;
Wen, Wu-Che ;
Chen, Peini ;
Guh, Jih-Hwa .
BIOCHEMICAL PHARMACOLOGY, 2010, 79 (02) :162-171
[6]   Dysregulation of glycogen synthase kinase-3β signaling in hepatocellular carcinoma cells [J].
Desbois-Mouthon, C ;
Eggelpoël, MJBV ;
Beurel, E ;
Boissan, M ;
Delélo, R ;
Cadoret, A ;
Capeau, J .
HEPATOLOGY, 2002, 36 (06) :1528-1536
[7]   Oncogene-specific activation of tyrosine kinase networks during prostate cancer progression [J].
Drake, Justin M. ;
Graham, Nicholas A. ;
Stoyanova, Tanya ;
Sedghi, Amir ;
Goldstein, Andrew S. ;
Cai, Houjian ;
Smith, Daniel A. ;
Zhang, Hong ;
Komisopoulou, Evangelia ;
Huang, Jiaoti ;
Graeber, Thomas G. ;
Witte, Owen N. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2012, 109 (05) :1643-1648
[8]  
Gedaly R, 2012, ANTICANCER RES, V32, P2531
[9]   TSC2 mediates cellular energy response to control cell growth and survival [J].
Inoki, K ;
Zhu, TQ ;
Guan, KL .
CELL, 2003, 115 (05) :577-590
[10]   TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth [J].
Inoki, Ken ;
Ouyang, Hongjiao ;
Zhu, Tianqing ;
Lindvall, Charlotta ;
Wang, Yian ;
Zhang, Xiaojie ;
Yang, Qian ;
Bennett, Christina ;
Harada, Yuko ;
Stankunas, Kryn ;
Wang, Cun-yu ;
He, Xi ;
MacDougald, Ormond A. ;
You, Ming ;
Williams, Bart O. ;
Guan, Kun-Liang .
CELL, 2006, 126 (05) :955-968