| PrefaceHepatocellular carcinoma (HCC) is one of the commonest malignant tumor in the world , has high mortality . It' s pathogenesis is mul-tifactor and multistep long - term complicatedly evolutive process including oncogene activation and tumor suppressor gene inactivation . Investigating hepatocellular carcinoma - related gene has important significance in prevention ,clinical diagnosis,clinical therapy of hepatocellular carcinoma . C - erbB2 gene encodes protein with activity of receptor tyrosine kinase , which belongs to subunit of epidermal growth factor receptor (EGFR) and participates in cellular growth and differentiation , ultimately is able to result in normal cellular malignancy transformation and malignant tumor development . Research in the world show that C - erbB2 expression consists in most hepatocellular carcinoma , but biological meaning of C - erbB2 gene amplification in hepatocellular carcinoma still keeps uncertain. In this experiment we detected C - erbB2 gene amplification and expression by differential PCR and immunity histochemistry technology ,and discussed relation betweeen amplification and expression of C - erbB2 gene and clinico-pathologic features in hepatocellular carcinoma.MaterialsHCC from 42 patients , which had been surgically resected at Department of Surgery , China Medical University , and these cases from 1993 to 2000 were examined . Hepatocellular carcinoma was confirmed by pathology. 42 patients included 36 men and 6 women , whose age was from 17 to 67 years ,mean age was 51 years . All specimen were fixed by formalin and embedded by paraffin . Histology grade of hepa-tocellular carcinoma adopted Edmondson grade; I level (high differentiation) ; II - IHlevel( median differentiation) ; IVlevel( poor differentiation ) , clinicopathological data were obtained by reviewing patients' cases and pathological reports. 10 normal liver samples in the same period were selected as reference.MethodsWe extracted DNA from paraffin tissue of hepatocellular carcinoma and normal liver, and then amplifyed C - erbB2 gene by differential PCR . We detected expression of C - erbB2 protein by SP method. Correlations betweeen amplification and expression of C ?erbB2 gene and clinicopathologic features were analyzed by chi - squared test.Results16 cases in 42 hepatocellular carcinoma had C ?erbB2 amplification, and C - erbB2 amplification had relations with HbsAg, tumour size, Edmondson grades ,clinical stages, hepatocirrhosis,exo -liver metastasis , whereas was independent of age, sex, AFP, the number of tumor nodule ,tumor capsule,portal vein cancer embolism. 19 case in 42 hepatocellular carcinoma had C - erbB2 expression, and C - erbB2expression had relations with HbsAg, tumour size,, Edmondson grades, clinical stages, portal vein cancer embolism, hepatocirrhosis, exo -liver metastasis ,whereas was independent of age,sex,AFP,the number of tumor nodule, tumor capsule. Relativity between C - erbB2 amplification and C - erbB2 expression had been found.DiscussionThe oncogene C - erbB2 , known as HER - 2/neu, a sort of V -erbB -related gene,locates on chromsome 17q21. C -erbB2 oncogene transcribes 4.8kb mRN A, encoding 185kd transmembrane glycoprotein which is customarily intituled as PI 85 protein. PI 85 belongs to sub-unit of epidermal growth factor receptor , which is a sort of receptor tyrosine kinase(RTK). With the increase of c - erbB2 protein level, the level of tyrosine residue locus phosphorylation of c - erbB2 protein also increase . The protein of phosphorylation activates five different signal transduction pass; PLC-r/ phosphatidyl inositol(PI)transit, PI kinase,SAT91/ISGF-3,ras/raf/MAPK as well as src protein family . Activation of ras and MAPK can stimulate C - jun and C - fos genetic transcription in early stage and accumulation of their mRN A, whereas C - jun and C - fos are oncogene of nucleus transcription factor . The activation of C - jun and C - fos improve level of nucleus transcription factor protein and phosphorylation , thereby result... |
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