INSULIN-LIKE GROWTH FACTOR-I BINDING IN HEPATOCYTES FROM HUMAN-LIVER, HUMAN HEPATOMA, AND NORMAL, REGENERATING, AND FETAL-RAT LIVER
INSULIN-LIKE GROWTH FACTOR-I BINDING IN HEPATOCYTES FROM HUMAN-LIVER, HUMAN HEPATOMA, AND NORMAL, REGENERATING, AND FETAL-RAT LIVER
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DOI：
10.1172/jci113451
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发表时间：
1988-04-01
影响因子：
15.9
通讯作者：
SINHA, MK
中科院分区：
文献类型：
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作者：
CARO, JF;POULOS, J;SINHA, MK
人肝癌细胞（HEP-G2）中的胰岛素样生长因子- i （IGF-I）除了对细胞生长有影响外，还通过其自身受体发挥短期代谢作用。我们已经证明，与HEP-G2细胞相比，正常的人肝细胞几乎没有igf - 1结合位点。由于生长速度是肝癌与正常肝脏的主要区别，我们询问正常肝脏在生理生长条件下是否可能表达IGF-I结合位点。事实上，尽管成年大鼠肝细胞的IGF-I结合位点与人类肝脏相似，但经过3天肝次全切除术后再生肝细胞的IGF-I结合位点增加了约6倍（P < 0.005），而来自胎儿肝的肝细胞的IGF-I结合位点增加了约1倍。增加了12倍（P < 0.005），达到与HEP-G2细胞相当的水平。125I型IGF-I与其受体结合的特异性通过针对IGF-I和胰岛素受体的单克隆抗体、未标记的IGF-I和胰岛素的竞争研究以及亲和标记实验证明。因此，如果igf - 1在成人肝脏中有任何短期代谢功能，也不是通过与自身受体的相互作用实现的。IGF-I对肝脏生长的自分泌调节似乎是可能的，因为IGF-I结合位点是在病理和生理生长条件下表达的。耦合这两种现象的机制还有待阐明。
Insulin-like growth factor-I (IGF-I) in human hepatoma cells (HEP-G2) has, in addition to its effect on cell growth, short-term metabolic effects acting through its own receptor. We have demonstrated that normal human hepatocytes, compared with HEP-G2 cells, have virtually no IGF-I binding sites. Because the rate of growth is the major difference between the hepatoma and the normal liver, we asked if normal liver might express IGF-I binding sites under physiologic growth conditions. Indeed, whereas adult rat hepatocytes have low IGF-I binding sites similar to those in human liver, hepatocytes from regeneratingliver after 3 d subtotal hepatectomy have an approximately sixfold increase (P < 0.005) and those from fetal rat liver a .apprx. 12-fold increase (P < 0.005), to levels comparable to those in the HEP-G2 cells. The specificity of 125I IGF-I binding to its receptor was demonstrated by competition studies with monoclonal antibodies directed toward the IGF-I and the insulin receptors, with unlabeled IGF-I and insulin and by affinity labeling experiments. Thus, if IGF-I has any short-term metabolic functions in the adult human liver, it is not through interaction with its own receptor. Autocrine regulation by IGF-I of liver growth appears possible since IGF-I binding sites are expressed under pathological and physiological conditions of growth. The mechanism that couples these two phenomena remains to be elucidated.