Rosewicz S, Weder M, Kaiser A, Riecken E O
Department of Gastroenterology, Medizinische Klinik and Poliklinik, Khnikum Benjamin Franklin, Berlin, Germany.
Gut. 1996 Aug;39(2):255-61. doi: 10.1136/gut.39.2.255.
The molecular mechanisms mediating the antiproliferative effects of interferon alpha on human pancreatic carcinoma cells are poorly understood.
To characterise the effects of interferon alpha on protein kinase C isoenzyme expression in interferon alpha sensitive and resistant human pancreatic tumour cell lines.
The ductal human pancreatic carcinoma cell lines Capan 1 and Capan 2 were investigated. Anchorage dependent and independent growth was determined by cell number and a human tumour clonogenic assay. Interferon alpha receptor expression was examined by reverse-transcriptase polymerase chain reaction and electrophoretic mobility shift assay. Protein kinase C isoenzyme expression was evaluated by western blotting using monospecific polyclonal antibodies.
Interferon alpha treatment results in a time and dose dependent inhibition of anchorage dependent and independent growth in Capan 1 cells while Capan 2 cells were not affected by interferon alpha. Both cell lines express interferon alpha receptor mRNA transcripts. Growth inhibition by interferon alpha in Capan 1 cells was paralleled by a profound decrease of protein kinase C alpha and zeta expression while these isoenzymes were unaffected in the interferon resistant cell line Capan 2.
Inhibition of protein kinase C isoenzyme expression might determine the sensitivity of a given pancreatic carcinoma to respond to the antiproliferative action of interferon alpha.
介导干扰素α对人胰腺癌细胞抗增殖作用的分子机制尚不清楚。
明确干扰素α对干扰素α敏感和耐药的人胰腺肿瘤细胞系中蛋白激酶C同工酶表达的影响。
研究了人胰腺导管癌细胞系Capan 1和Capan 2。通过细胞计数和人肿瘤克隆形成试验测定贴壁依赖性和非依赖性生长。通过逆转录聚合酶链反应和电泳迁移率变动分析检测干扰素α受体表达。使用单特异性多克隆抗体通过蛋白质印迹法评估蛋白激酶C同工酶表达。
干扰素α处理导致Capan 1细胞中贴壁依赖性和非依赖性生长受到时间和剂量依赖性抑制，而Capan 2细胞不受干扰素α影响。两种细胞系均表达干扰素α受体mRNA转录本。干扰素α对Capan 1细胞生长的抑制伴随着蛋白激酶Cα和ζ表达的显著降低，而这些同工酶在干扰素耐药细胞系Capan 2中未受影响。
蛋白激酶C同工酶表达的抑制可能决定了给定胰腺癌对干扰素α抗增殖作用的反应敏感性。
