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人原发性肝癌的癌基因谱

A SPECTRUM OF ACTIVATED PROTO-ONCOGENES IN HUMAN PRIMARY HEPATIC CANCER

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【摘要】 <正> 肿瘤发生是多病因参与和多阶段的过程。因此,从理论上推测应有多种激活的原癌基因参与。由于各种癌的组织发生不同,推测各种肿瘤应有一个癌基因谱的参与,不同肿瘤中可以有所差异。 从发现人原发性肝癌N-ras作为一种转化基因

【Abstract】 More than 20 proto-oncogenes, growth factor and receptor genes were analyzedfor their mRNA expression in human primary hepatic cancer (PHC) and cancer-surrounding liver tissues. It has been demonstrated that N-ras, c-myc, c-fms (CSF1receptor), c-ets-2, p53, c-fos and IGF-Ⅱ were over-expresssed at mRNA level in PHCand tumor-surrounding liver samples. However, only the expression of N-ras, c-fmsand c-myc were higher than tumor-surrounding liver tissues in the same patients. ThemRNA expression of other 4 genes were at various level in cancer tissues as comparedwith their surrounding liver tissues. The mRNA expression of the above 7 proto-oncogenes and related genes werefurther analyzed in tumor and tumor surrounding liver tissue from 5 PHC patients.Itwas demonstrated that N-ras, c-myc andc-fms were over expressed in most cases ofcancer tissues. Furthermore, among the nuclear family members of proto-oncogenes,such as c-fos, c-myc, c-ets-2, p53, at least two of them were over-expressed in cancertissues, implicating a complementary effect among these nuclear mitogen-responsegenes. Since IGF-Ⅱ has been demonstrated as a fetal growth factor stimulating thegrowth of liver, the increase of IGF-Ⅱ expression might indicate a mechanism ofautocrine involved in liver carcinogenesis. Moreover, the over-expressed CSFI receptor(c-fms) might further stimulate the cell growth increasing interaction with theirrelevant growth factor CSF1. A whole N-ras gene has been cloned directly from a genomic library constructedfrom one PHC specimen (G5). The trasfection assay indicated that the cloned N-rasgene had high transforming activity (>1000 foci/ug DNA).It is the first demonstrationof a transforming ras gene cloned directly from a human primary tumor.

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