Vardy D A, Kari C, Lazarus G S, Jensen P J, Zilberstein A, Plowman G D, Rodeck U
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104, USA.
J Cell Physiol. 1995 May;163(2):257-65. doi: 10.1002/jcp.1041630206.
Autocrine activation of the epidermal growth factor (EGF) receptor on keratinocytes has been recognized as an important growth regulatory mechanism involved in epithelial homeostasis, and, possibly, hyperproliferative diseases. Insulin-like growth factor (IGF)-1 and insulin have been shown to be paracrine keratinocyte mitogens that bind to the type I IGF receptor which is expressed on actively proliferating keratinocytes in situ. In this report, we demonstrate that IGF-1/insulin induced production of keratinocyte-derived autocrine growth factors that bind to the EGF receptor. Increased steady-state mRNA levels for transforming growth factor alpha (TGF-alpha) and for amphiregulin (AR) were observed upon incubation of keratinocytes with mitogenic concentrations of IGF-1. IGF-1 also induced production and secretion of TGF-alpha and AR proteins as detected by immunoassays. An EGF receptor antagonistic monoclonal antibody abolished the mitogenic effect of IGF-1 on cultured keratinocytes. These results suggest that stimulation of keratinocyte growth of IGF-1 requires activation of an EGF receptor-mediated autocrine loop.
角质形成细胞上表皮生长因子（EGF）受体的自分泌激活已被认为是参与上皮内稳态以及可能参与增生性疾病的重要生长调节机制。胰岛素样生长因子（IGF）-1和胰岛素已被证明是旁分泌角质形成细胞有丝分裂原，它们与I型IGF受体结合，该受体在原位活跃增殖的角质形成细胞上表达。在本报告中，我们证明IGF-1/胰岛素诱导产生与EGF受体结合的角质形成细胞源性自分泌生长因子。用促有丝分裂浓度的IGF-1孵育角质形成细胞后，观察到转化生长因子α（TGF-α）和双调蛋白（AR）的稳态mRNA水平增加。免疫测定检测到IGF-1还诱导TGF-α和AR蛋白的产生和分泌。一种EGF受体拮抗单克隆抗体消除了IGF-1对培养角质形成细胞的促有丝分裂作用。这些结果表明，IGF-1刺激角质形成细胞生长需要激活EGF受体介导的自分泌环。
