Powell D, Lee P D, DePaolis L A, Morris S L, Suwanichkul A
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030.
Growth Regul. 1993 Mar;3(1):11-3.
Insulin-like growth factor binding protein-1 (IGFBP-1) serum levels are increased by glucocorticoids and glucagon, and are decreased by insulin; these effects seem to reflect changes in hepatic IGFBP-1 expression. Human HEP G2 hepatoma cells respond to cAMP or insulin with stimulation or inhibition of IGFBP-1 expression, respectively; however, dexamethasone alone does not stimulate IGFBP-1 expression. Studies presented here show that in the presence of cAMP and theophylline, nontransfected HEP G2 cells respond to further addition of dexamethasone with a approximately 70% rise in IGFBP-1 mRNA levels, and HEP G2 cells transfected with IGFBP-1 promoter constructs respond to further addition of dexamethasone with a approximately 70% rise in IGFBP-1 protein levels and a approximately 9-fold rise in IGFBP-1 promoter activity. The stimulatory effect of dexamethasone and cAMP, conferred to the IGFBP-1 promoter between 357 and 103 base pairs 5' to the mRNA cap site, is inhibited by insulin. Thus, the cis elements necessary to confer multihormonal regulation of IGFBP-1 expression appear to reside in a short stretch of DNA just upstream from the IGFBP-1 transcription start site.
胰岛素样生长因子结合蛋白-1（IGFBP-1）的血清水平会因糖皮质激素和胰高血糖素而升高，因胰岛素而降低；这些作用似乎反映了肝脏中IGFBP-1表达的变化。人肝癌细胞系HEPG2对cAMP或胰岛素分别有刺激或抑制IGFBP-1表达的反应；然而，单独使用地塞米松并不会刺激IGFBP-1表达。本文的研究表明，在存在cAMP和茶碱的情况下，未转染的HEPG2细胞在进一步添加地塞米松后，IGFBP-1 mRNA水平会升高约70%，而用IGFBP-1启动子构建体转染的HEPG2细胞在进一步添加地塞米松后，IGFBP-1蛋白水平会升高约70%，IGFBP-1启动子活性会升高约9倍。地塞米松和cAMP对IGFBP-1启动子的刺激作用（在mRNA帽位点上游5'端357至103个碱基对之间赋予IGFBP-1启动子）会被胰岛素抑制。因此，赋予IGFBP-1表达多激素调节所需的顺式元件似乎位于IGFBP-1转录起始位点上游的一小段DNA中。
