Effect of heparin and liver heparan sulphate on interaction of HepG2-derived transcription factors and their cis-acting elements:: altered potential of hepatocellular carcinoma heparan sulphate
Effect of heparin and liver heparan sulphate on interaction of HepG2-derived transcription factors and their cis-acting elements:: altered potential of hepatocellular carcinoma heparan sulphate
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DOI：
10.1042/0264-6021:3500245
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发表时间：
2000-08-15
影响因子：
4.1
通讯作者：
Kovalszky, I
中科院分区：
文献类型：
--
作者：
Dudás, J;Ramadori, G;Kovalszky, I
恶性肿瘤中的蛋白聚糖组装发生了深刻的变化。这些变化的意义还没有得到很好的理解;特别是，它们在核监管中的作用是一个辩论的话题。研究了肝素和肝癌硫酸乙酰肝素（HS）改变DNA-转录因子相互作用的能力，以提供有关细胞核中糖胺聚糖（GAG）调节潜力的进一步证据。体外和体内实验表明，肝素和HS能够抑制转录因子与其共有寡核苷酸元件的相互作用。在研究的五个转录因子中，AP-1，SP-1，ETS-1和核因子KB被证明对肝素和硫酸乙酰肝素敏感，而TFIID在体外或体内系统中几乎没有被抑制。有趣的是，来自瘤周肝脏的HS比肝素有效5倍，肝癌HS比肝HS有效性低，但其活性与肝素相当。这些结果表明，GAG链的结构差异强烈影响其生物学行为。在恶性肿瘤中，其公认的功能活性的丧失可能促进不受控制的生长和有利于肿瘤过程的基因表达的发展。
Proteoglycan assembly in malignant tumours is subject to profound changes. The significance of these alterations is not well understood; especially, their role in nuclear regulation is a topic for debate. The capacity of heparin and liver carcinoma heparan sulphate (HS) to alter DNA-transcription factor interactions has been studied to provide further evidence concerning the regulatory potential of glycosaminoglycan (GAG) in the nucleus. Experiments both in vitro and in vivo indicated that heparin and HS are capable of inhibiting the interaction of transcription factors with their consensus oligonucleotide elements. Among five transcription factors studied, AP-1, SP-1, ETS-1 and nuclear factor KB proved to be sensitive to heparin and heparan sulphate, whereas TFIID was hardly inhibited in either in vitro or in vivo systems. Interestingly, HS from peritumoral liver was five times more effective than heparin, Liver carcinoma HS was less effective than liver HS, but its activity was comparable with that of heparin. These results indicate that the structural differences of GAG chains strongly influence their biological behaviour. The loss of their recognized functional activity in malignant rumours might promote the development of uncontrolled growth and gene expression favouring the neoplastic process.