Biedler J L, Chang T D, Meyers M B, Peterson R H, Spengler B A
Cancer Treat Rep. 1983 Oct;67(10):859-67.
Studies of Chinese hamster and mouse cells with high levels of acquired resistance to dactinomycin, daunorubicin, or vincristine have shown that these different permeability mutants all display similar phenotypic alterations: dramatic changes toward normal cell morphology and growth behavior and substantially reduced oncogenic potential. All three resistant cell types show increased expression of a high molecular weight plasma membrane glycoprotein species, gp150. Uniquely, vincristine-resistant cells contain gene amplification-associated chromosome abnormalities (homogeneously staining regions or double minute chromosomes), and they oversynthesize a low molecular weight cytosolic protein (V19). Cells grown in the absence of drug are phenotypically unstable. Revertant cells decline in resistance, length or number of homogeneously staining regions or double minute chromosomes, and expression of gp150 and V19. These proteins are thus candidate products of amplified genes which may or may not be manifested cytogenetically. The phenomena of drug resistance and reverse transformation are currently being addressed in protein phosphorylation studies.
对中国仓鼠和小鼠细胞进行的研究表明，这些细胞对放线菌素、柔红霉素或长春新碱具有高度获得性抗性，这些不同的通透性突变体均表现出相似的表型改变：细胞形态和生长行为向正常细胞发生显著变化，致癌潜力大幅降低。所有三种抗性细胞类型均显示一种高分子量质膜糖蛋白gp150的表达增加。独特的是，长春新碱抗性细胞含有与基因扩增相关的染色体异常（均匀染色区或双微体染色体），并且它们过度合成一种低分子量胞质蛋白（V19）。在无药物条件下生长的细胞在表型上不稳定。回复细胞的抗性、均匀染色区或双微体染色体的长度或数量以及gp150和V19的表达均下降。因此，这些蛋白质可能是扩增基因的候选产物，其可能在细胞遗传学上表现出来，也可能不表现出来。目前正在蛋白质磷酸化研究中探讨耐药性和反向转化现象。
