Heparin and hormonal regulation of mRNA synthesis and abundance of autocrine growth factors: relevance to clonal growth of tumors.
Heparin and hormonal regulation of mRNA synthesis and abundance of autocrine growth factors: relevance to clonal growth of tumors.
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肝素和 mRNA 合成的激素调节以及自分泌生长因子的丰度：与肿瘤克隆生长的相关性。
DOI：
10.1128/mcb.11.1.108-116.1991
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发表时间：
1991
影响因子：
5.3
通讯作者：
Reid,LM
中科院分区：
文献类型：
--
作者：
Zvibel,I;Halay,E;Reid,LM
具有肝素样糖胺聚糖链的硫酸乙酰肝素蛋白聚糖的高度硫酸化、肝素样物质是细胞外基质组分，其在生长停滞的肝细胞中与质膜结合。肝素被发现抑制生长和降低克隆生长效率的HepG2，一个最小的偏差，人肝癌细胞系。硫酸乙酰肝素，密切相关的糖胺聚糖存在于生长的肝细胞周围的细胞外基质中，对HepG2细胞的生长速率或克隆生长效率没有影响。肝素和硫酸乙酰肝素对两种低分化、高转移性肝癌细胞系SK-Hep-1和PLC/PRF/5的生长速率或克隆生长效率均无任何影响。肝素对HepG2细胞生长的抑制与胰岛素样生长因子II（IGF II）和转化生长因子β（TGF β 1）的mRNA合成和丰度的变化相关。HepG2细胞表达高基础水平的编码IGF II和TGF β 1的mRNA，其通过转录和转录后机制被特异性肝素-激素组合诱导至更高水平。对于IGF II和TGF β，调节是多因素的。在转录方面，IGF II受胰岛素、胰高血糖素和生长激素联合肝素的累加效应调节; TGF β主要受胰岛素和生长激素联合肝素的协同效应调节。转录后，IGF II 4.5-和3.7-kb转录物的mRNA丰度受到胰岛素的影响。肝素诱导的所有IGF II的转录也依赖于三碘代酪氨酸和催乳素，但它是未知的，无论是通过转录或转录后机制的肝素诱导。肝素-胰岛素组合在转录后调节TGF β。低分化肝癌细胞系PLC/PRF/5和SK-Hep-1不表达或组成性表达低基础水平的IGF I、IGF II和TGF β，其mRNA合成和丰度显示对任何肝素-激素组合无反应。我们讨论的数据作为证据，基质化学是一个变量，确定自分泌生长因子基因的表达和生物反应。
Highly sulfated, heparinlike species of heparan sulfate proteoglycans, with heparinlike glycosaminoglycan chains, are extracellular matrix components that are plasma membrane bound in growth-arrested liver cells. Heparins were found to inhibit the growth and lower the clonal growth efficiency of HepG2, a minimally deviant, human hepatoma cell line. Heparan sulfates, closely related glycosaminoglycans present in the extracellular matrix around growing liver cells, had no effect on the growth rate or clonal growth efficiency of HepG2 cells. Neither heparins nor heparan sulfates had any effect on the growth rate or clonal growth efficiency of two poorly differentiated, highly metastatic hepatoma cell lines, SK-Hep-1 and PLC/PRF/5. Heparin’s inhibition of growth of HepG2 cells correlated with changes in the mRNA synthesis and abundance of insulinlike growth factor II (IGF II) and transforming growth factor beta (TGFfl). HepG2 cells expressed high basal levels of mRNAs encoding IGF II and TGFfl that were inducible, through transcriptional and posttranscriptional mechanisms, to higher levels by specific heparin-hormone combinations. For both IGF II and TGFβ, the regulation was multifactorial. Transcriptionally, IGF II was regulated by the additive effects of insulin, glucagon, and growth hormone in combination with heparin; TGFβ was regulated primarily by the synergistic effects of insulin and growth hormone in combination with heparin. Posttranscriptionally, the mRNA abundance of the IGF II 4.5- and 3.7-kb transcripts was affected by insulin. Heparin induction of all IGF II transcripts was also dependent on triiodotyronine and prolactin, but it is unknown whether their induction by heparin was via transcriptional or posttranscriptional mechanisms. Heparin-insulin combinations regulated TGFβ posttranscriptionally. The poorly differentiated hepatoma cell lines PLC/PRF/5 and SK-Hep-1 either did not express or constitutively expressed low basal levels of IGF I, IGF II, and TGFβ, whose mRNA synthesis and abundance showed no response to any heparin-hormone combination. We discuss the data as evidence that matrix chemistry is a variable determining the expression of autocrine growth factor genes and the biological responses to them.