Krane J F, Murphy D P, Carter D M, Krueger J G
Laboratory for Investigative Dermatology, Rockefeller University, New York, New York 10021-6399.
J Invest Dermatol. 1991 Apr;96(4):419-24. doi: 10.1111/1523-1747.ep12469799.
The epidermal growth factor (EGF) receptor pathway is an important mediator of keratinocyte growth in vitro and both receptor and ligand components of this pathway are abnormally expressed in hyperproliferative epidermis. The purpose of this study was to examine interactions between the EGF receptor pathway and the insulin-like growth factor I/somatomedin C (IGF-I) receptor pathway in modulating the growth of cultured normal human keratinocytes. Short-term growth of keratinocytes in a chemically defined medium demonstrated that neither EGF nor IGF-I alone could support significant keratinocyte spreading or proliferation, but that a combination of EGF with IGF-I or high-dose insulin could. IGF-I or high-dose insulin transmodulates keratinocyte EGF receptor expression via the IGF-I receptor in a dose- and time-dependent manner, increasing EGF receptor binding an average of 1.8 times up to a maximum of fourfold without altering EGF binding affinity. Staining of normal human epidermis with an IGF-I receptor specific monoclonal antibody demonstrates that IGF-I receptors localize to the basal proliferative cell compartment, suggesting that IGF-I receptor and EGF receptor pathway interactions may play a role in the regulation of epidermal growth and in the pathogenesis of hyperproliferative skin diseases.
表皮生长因子（EGF）受体途径是体外角质形成细胞生长的重要介质，该途径的受体和配体成分在增殖过度的表皮中均有异常表达。本研究的目的是检测EGF受体途径与胰岛素样生长因子I/生长调节素C（IGF-I）受体途径在调节培养的正常人角质形成细胞生长过程中的相互作用。角质形成细胞在化学成分明确的培养基中的短期生长表明，单独的EGF或IGF-I均不能支持角质形成细胞显著的铺展或增殖，但EGF与IGF-I或高剂量胰岛素联合使用则可以。IGF-I或高剂量胰岛素通过IGF-I受体以剂量和时间依赖性方式调节角质形成细胞EGF受体的表达，在不改变EGF结合亲和力的情况下，使EGF受体结合平均增加1.8倍，最高可达四倍。用IGF-I受体特异性单克隆抗体对正常人表皮进行染色显示，IGF-I受体定位于基底增殖细胞区室，提示IGF-I受体与EGF受体途径的相互作用可能在表皮生长调节及增殖过度性皮肤病的发病机制中发挥作用。
