肝细胞恶性转化过程中胰岛素样生长因子-I受体的动态表达与改变

严晓娣; 董志珍; 陈洁; 邱历伟; 吴玮; 姚登福

肝细胞恶性转化过程中胰岛素样生长因子-I受体的动态表达与改变

南通大学附属医院临床医学研究中心

基金项目:

江苏省临床医学科技专项(BL2012053)；南通市科技项目(HS2012039、K2010026)；

详细信息

中图分类号: R735.7
计量
- 文章访问数: 3105
- HTML全文浏览量: 10
- PDF下载量: 731
- 被引次数: 0
出版历程
- 出版日期: 2013-03-20

Dynamic expression profile of the insulin-like growth factor-1 receptor during malignant transformation of hepatocytes

Research funding:

摘要

摘要:
目的观察肝细胞恶性转化过程中胰岛素样生长因子-I受体（IGF-IR）的动态表达与改变特征。方法以2-乙酰氨基芴（2-FAA）喂饲雄性SD大鼠诱发肝癌发生,分别观察肝细胞形态学、肝及血IGF-1R的动态变化。以免疫组化法观察肝组织IGF-1R表达,以RT-PCR扩增IGF-1R mRNA表达片段并经测序证实,从基因转录和蛋白水平上分析与肝细胞恶性转化的相互关系。结果诱癌过程中肝细胞出现颗粒样变性、癌前病变到肝癌形成的动态变化,伴肝核酸代谢旺盛,肝IGF-IR表达异常;肝IGF-IR阳性率（%）、肝IGF-IR mRNA阳性率（%）、肝IGF-IR比浓度（ng/mg肝组织）和血IGF-IR（ng/ml）分别为:对照组0、0、0.63±0.17和1.33±0.47;变性组50、61.1、0.65±0.2和1.51±0.46;癌前组88.9、100、0.66±0.14和1.92±0.29;癌变组100、100、0.96±0.09和2.43±0.57。IGF-IR在转录或蛋白水平上呈梯度表达,癌变组显著高于其他组（P<0.01）,且肝和血IGF-IR呈显著正相关（r=0.91,t=14.2...
- 癌,肝细胞 /
- 受体,IGF1型 /
- 基因扩增 /
- 序列分析,RNA
Abstract:
Objective To determine the dynamic expression pattern and investigate the mechanisms underlying modified expression of insulin-like growth factor-1 receptor (IGF-1R) during malignant transformation of hepatocytes.Methods The N-2-fluorenylacetamide-induced liver cancer model was established in male Sprague-Dawley rats.Uninduced rats served as controls.Morphological changes were observed in livers by histological analysis.Dynamic changes in liver and serum expression of IGF-1R were analyzed and quantitated by immunohistochemistry, immunoassays, and RT-PCR with DNA sequencing.The relation between IGF-1R expression and malignant transformation of hepatocytes was investigated at both the gene transcription and protein expression levels using rank correlation analysis.Results The 2-FAA-induced rat hepatocytes showed remarkable morphologic alterations, including granule-like degeneration and other features of precancerous to hepatoma formation, which paralleled with increases in IGF-1R expression.Comparison of the control rats, precancerous rats, degenerated rats, and hepatoma rats indicated differential profiles of liver IGF-IR (0, 88.9%, 50.0%, and 100%) , IGF-IR mRNA (0, 100%, 61.1%, and 100 %) , specific IGF-IR concentration (0.63±0.17, 0.66±0.14, 0.65±0.2, and 0.96±0.09, ng/mg wet liver) , and serum IGF-IR level (1.33±0.47, 1.92±0.29, 1.51±0.46, and 2.43±0.57 ng/ml) .The serum IGF-1R expression was significantly higher in the hepatoma group than in any of other groups (gene transcription and protein levels, P<0.01) .A positive relationship was found between liver and sera levels of IGF-1R (r=0.91, t=14.222, P<0.01) .Conclusion IGF-1R may participate in hepatocyte canceration.Overexpression of IGF-1R may represent a useful early marker to identify and monitor malignant transformation of hepatocytes.
- carcinoma /
- hepatocellular /
- receptor /
- IGF type 1

HTML全文

参考文献(17)

[1]Aravalli RN, Steer CJ, Cressman EN.Molecular mechanisms ofhepatocellular carcinoma[J].Hepatology, 2008, 48 (6) :2047-2063.

[2]Zhang HJ, Yao DF, Qin CL.The role of annexin A2 in the devel-opment and progression of hepatocellular carcinoma[J].J ClinHepatol, 2011, 27 (7) :772-778. (in Chinese) 张海健, 姚登福, 秦呈林.膜联蛋白A2过表达在肝细胞癌发生发展中的作用[J].临床肝胆病杂志, 2011, 27 (7) :772-778.

[3]Rehem RN, El-Shikh WM.Serum IGF-1, IGF-2 and IGFBP-3 as parameters in the assessment of liver dysfunction in patientswith hepatic cirrhosis and in the diagnosis of hepatocellular carcino-ma[J].Hepatogastroenterology, 2011, 58 (107-108) :949-954.

[4]Qian J, Yao D, Dong Z, et al.Characteristics of hepatic igf-ii ex-pression and monitored levels of circulating igf-ii mRNA in metas-tasis of hepatocellular carcinoma[J].Am J Clin Pathol, 2010, 134 (5) :799-806.

[5]Hoshida Y.Molecular signatures and prognosis of hepatocellularcarcinoma[J].Minerva Gastroenterol Dietol, 2011, 57 (3) :311-322.

[6]Wang YC, Liu YF, Zhu RP, et al.Expression of histone deacetylase 1and matrix metalloproteinase-2 in hepatocellular carcinoma and its sig-nificance[J].J Clin Hepatol, 2012, 28 (4) :276-278, 288. (in Chi-nese) 王迎春, 刘炎芳, 朱瑞萍, 等.组蛋白去乙酰化酶1及基质金属蛋白酶-2在肝细胞癌组织中的表达及意义[J].临床肝胆病杂志, 2012, 28 (4) :276-278, 288.

[7]Aleem E, Nehrbass D, Klimek F, et al.Upregulation of the insulinreceptor and type I insulin-like growth factor receptor are early e-vents in hepatocarcinogenesis[J].Toxicol Pathol, 2011, 39 (3) :524-543.

[8]Breuhahn K, Schirmacher P.Reactivation of the insulin-like growthfactor-II signaling pathway in human hepatocellular carcinoma[J].World J Gastroenterol, 2008, 14 (11) :1690-1698.

[9]Qiu LW, Yao DF, Zong L, et al.Abnormal expression of insulin-like growth factor-II and its dynamic quantitative analysis at differentstages of hepatocellular carcinoma development[J].Hepatobiliary Pan-creat Dis Int, 2008, 7 (4) :406-411.

[10]Ubagai T, Kikuchi T, Fukusato T, et al.Aflatoxin B1 modulatesthe insulin-like growth factor-2 dependent signaling axis[J].Toxicol In Vitro, 2010, 24 (3) :783-789.

[11] Weng CJ, Hsieh YH, Tsai CM, et al.Relationship of insulin-likegrowth factors system gene polymorphisms with the susceptibility andpathological development of hepatocellular carcinoma[J].Ann SurgOncol, 2010, 17 (7) :1808-1815.

[12]Nussbaum T, Samarin J, Ehemann V, et al.Autocrine insulin-like growth factor-II stimulation of tumor cell migration is a pro-gression step in human hepatocarcinogenesis[J].Hepatology, 2008, 48 (1) :146-156.

[13]Freise C, Ruehl M, Erben U, et al.A hepatoprotective Lindera ob-tusiloba extract suppresses growth and attenuates insulin like growthfactor-1 receptor signaling and NF-kappaB activity in human liv-er cancer cell lines[J].BMC Complement Altern Med, 2011, 11 (1) :39-46.

[14]El Tayebi HM, Salah W, El Sayed IH, et al.Expression of insulin-like growth factor-II, matrix metalloproteinases, and their tissue in-hibitors as predictive markers in the peripheral blood of HCC patients[J].Biomarkers, 2011, 16 (4) :346-354.

[15]Lu YY, Yao DF, Wu XH, et al.Expression of insulin-like growthfactor-1 receptor and its clinical pathological characteristics in hu-man hepatocelullar carcinoma and its pericarcinoma[J〗.J NantorgUniv (Med Sci) , 2008, 28 (3) :169-171. (in Chinese) 陆园园, 姚登福, 吴信华, 等.肝癌及癌旁组织IGF-I受体表达及临床病理学特征[J].南通大学学报 (医学版) , 2008, 28 (2) :169-171.

[16]Yao WF, Liu JW, Sheng GL, et al.Blockade of IGF-IR exertsanticancer effects in hepato-cellular carcinoma[J].Mol Med Re-port, 2011, 4 (4) :719-722.

[17]Tovar V, Alsinet C, Villanueva A, et al.IGF activation in a molec-ular subclass of hepato-cellular carcinoma and pre-clinical effi-cacy of IGF-1R blockage[J].J Hepatol, 2010, 52 (4) :550-559.

施引文献

资源附件(0)

访问统计