SOD2 - A NEW TYPE OF TUMOR-SUPPRESSOR GENE

SOD2 - A NEW TYPE OF TUMOR-SUPPRESSOR GENE
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DOI:
10.1002/ijc.2910510323
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发表时间:
1992-05-28
影响因子:
6.4
通讯作者:
DUTRILLAUX, B
DUTRILLAUX, B
中科院分区:
医学1区
文献类型:
--
作者:
BRAVARD, A;SABATIER, L;DUTRILLAUX, B

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对6个SV40转化的人成纤维细胞系(TF)和未转化的人成纤维细胞系(NF)的超氧化物歧化酶(SOD)1和2的活性与mRNA和染色体含量的相关性进行了分析。总的超氧化物歧化酶活性基本不变,但SOD2/SOD1值明显低于对照。SOD2活性的降低与低mRNA含量以及各种染色体重排的存在有关,这些重排导致了基因定位的6号染色体长臂的缺失。相反,携带SOD1基因的21号染色体未发现缺失,SOD1活性较高。这表明在转铁蛋白中,SOD2的活性在很大程度上取决于基因的剂量。有人提出,超氧化物歧化酶活性可能与细胞增殖呈负相关,特别是SOD2活性与细胞分化有关。因此,SOD2基因在细胞转化过程中发生了一系列事件,包括基因失控、染色体(基因)缺失、低mRNA和蛋白质含量、低酶活性以及生长优势的获得,这使得SOD2基因可能成为一种新型的肿瘤抑制基因。
The activity of superoxide dismutases (SOD) 1 and 2 was analysed in correlation with mRNA and chromosome content in 6 SV40-transformed (TF) and in non-transformed (NF) human fibroblast cell lines. Total SOD activity was fairly constant, whereas the ratio SOD2/SOD1 was much lower in TF than in NF. The decrease in SOD2 activity was correlated with a low mRNA content, and with the presence of various chromosomal rearrangements leading to deletions of the long arm of chromosome 6 where the gene is mapped. In contrast, chromosome 21, carrying the gene for SOD1, was not found to be deficient and the SOD1 activity was high. This shows that in TF, the activity of SOD2 is largely determined by gene dosage. It has been proposed that SOD activity could be inversely correlated with cell proliferation, and that SOD2 activity, in particular, was related to cell differentiation. Thus, there is a cascade of events occurring in cell transformation, involving gene deregulation, chromosome (gene) deletion, low mRNA and protein content, low enzyme activity, and acquisition of growth advantage which makes the SOD2 gene a possible new type of tumor-suppressor gene.