Warenius H M, Seabra L A, Maw P
Human Tumor Biology Group, University of Liverpool, UK.
Int J Cancer. 1996 Jul 17;67(2):224-31. doi: 10.1002/(SICI)1097-0215(19960717)67:2<224::AID-IJC13>3.0.CO;2-B.
Although several oncogenes, including c-myc, ras and c-raf-1, have been implicated in cellular resistance to ionising radiation, there is less information relating oncogene expression to cis-diamminedichloroplatinum (CDDP) resistance. However, transfection of c-myc or v-H-ras and activation of protein kinase C (PKC), which contributes to the RAF-1, MAP kinase signal transduction pathway, can influence therapeutic response to CDDP. Activation of PKC increases CDDP sensitivity, whilst transfected c-myc or v-H-ras induce CDDP resistance. We have previously reported that human in vitro cell lines show different patterns of sensitivity to CDDP and 4 MeV X-irradiation. In these cells radiation sensitivity is related to high levels of expression of the C-raf-1 proto-oncogene. We thus predicted that cells sensitive to CDDP might show a different relationship to c-raf-1 expression. In addition, because cyclin D1 expression can be upregulated by the myc or ras oncogenes, we also chose to study putative relationships between cyclin D1 protein levels and intrinsic cellular sensitivity to CDDP and gamma-irradiation. We report that in the 16 human cell lines which we have studied, high cyclin D1 expression is related to CDDP resistance but has no relationship with radiation responsiveness, whereas high c-raf-1 expression, although related to radiosensitivity has no relationship with CDDP responsiveness.
尽管包括c-myc、ras和c-raf-1在内的几种癌基因与细胞对电离辐射的抗性有关，但关于癌基因表达与顺二氨二氯铂（CDDP）抗性之间的信息较少。然而，c-myc或v-H-ras的转染以及蛋白激酶C（PKC）的激活（其有助于RAF-1、丝裂原活化蛋白激酶信号转导途径）可影响对CDDP的治疗反应。PKC的激活增加了CDDP敏感性，而转染的c-myc或v-H-ras则诱导CDDP抗性。我们之前报道过人源体外细胞系对CDDP和4 MeV X射线照射表现出不同的敏感性模式。在这些细胞中，辐射敏感性与C-raf-1原癌基因的高表达水平有关。因此我们预测，对CDDP敏感的细胞可能与c-raf-1表达存在不同的关系。此外，由于细胞周期蛋白D1的表达可被myc或ras癌基因上调，我们还选择研究细胞周期蛋白D1蛋白水平与细胞对CDDP和γ射线照射的内在敏感性之间的假定关系。我们报道，在我们研究的16个人源细胞系中，细胞周期蛋白D1的高表达与CDDP抗性有关，但与辐射反应性无关，而c-raf-1的高表达虽然与放射敏感性有关，但与CDDP反应性无关。
