Mantzouris N M, Kaplan J, Clark G, Hise M K
Department of Internal Medicine, University of Maryland Medical School, Baltimore.
Am J Kidney Dis. 1993 Dec;22(6):858-64. doi: 10.1016/s0272-6386(12)70346-3.
The importance of receptor expression and protein kinase C to epidermal growth factor (EGF)-induced cell proliferation was studied in LLC-PK1 kidney cells. These cells have both high- and low-affinity binding sites for EGF. Neither transforming growth factor-beta nor tumor necrosis factor altered EGF receptor expression. On the other hand, retinoic acid induced a concentration-dependent increase in EGF binding that was maximal at 1 mumol/L. One micromolar of retinoic acid increased EGF binding from 0.38 +/- 0.01 fmol/10(6) cells in controls to 1.10 +/- 0.03 fmol/10(6) in treated cells at 18 hours (n = 8, P < 0.001). The increase in binding was the result of an increase in the Bmax of the high-affinity receptor. The upregulation of the EGF receptor induced by retinoic acid was associated with enhanced EGF-induced growth promotion. A 45-minute incubation of cells with phorbol 12-myristate 13-acetate caused a concentration-dependent decrease in EGF binding that was prevented by a 40-hour, 2 mumol/L pre-exposure to phorbol 12-myristate 13-acetate; 10(-8) mol/L EGF also caused a downregulation of the EGF receptor that was not prevented by phorbol 12-myristate 13-acetate or retinoic acid. Downregulation of protein kinase C did not interfere in the capacity of EGF to induce growth in these cells. These studies demonstrate that EGF receptor upregulation plays an important role in the control of EGF-induced cell growth. Protein kinase C regulates EGF binding in these cells; however, it is not necessary for EGF-induced growth promotion or receptor downregulation.
在LLC - PK1肾细胞中研究了受体表达和蛋白激酶C对表皮生长因子（EGF）诱导的细胞增殖的重要性。这些细胞对EGF具有高亲和力和低亲和力结合位点。转化生长因子 - β和肿瘤坏死因子均未改变EGF受体的表达。另一方面，视黄酸诱导EGF结合呈浓度依赖性增加，在1μmol/L时达到最大值。1μmol/L的视黄酸使EGF结合在18小时时从对照中的0.38±0.01 fmol/10⁶细胞增加到处理细胞中的1.10±0.03 fmol/10⁶（n = 8，P < 0.001）。结合的增加是高亲和力受体Bmax增加的结果。视黄酸诱导的EGF受体上调与EGF诱导的生长促进增强相关。用佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯孵育细胞45分钟导致EGF结合呈浓度依赖性降低，而40小时、2μmol/L预先暴露于佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯可阻止这种降低；10⁻⁸mol/L EGF也导致EGF受体下调，而佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯或视黄酸不能阻止这种下调。蛋白激酶C的下调并不干扰EGF在这些细胞中诱导生长的能力。这些研究表明，EGF受体上调在控制EGF诱导的细胞生长中起重要作用。蛋白激酶C调节这些细胞中的EGF结合；然而，它对于EGF诱导的生长促进或受体下调不是必需的。
