Smith G J, Bell W N, Grisham J W
Department of Pathology, University of North Carolina, Chapel Hill 27599.
Cancer Res. 1993 Feb 1;53(3):500-8.
Seventy-five clonal populations of morphologically transformed 10T1/2 cells were established from independent Type II and Type III foci that were of spontaneous origin or were induced by the carcinogenic agents N-methyl-N'-nitro-N-nitrosoguanidine, benzo(a)pyrene diol epoxide-I, and 3-methylcholanthrene. Clonal populations were characterized for expression of selected transformation phenotypes, including growth to elevated saturation density before cessation of proliferation, anchorage independence, ability to reconstruct foci when plated in the presence of wild-type 10T1/2 cells, and tumorigenicity. Forty-one % of the clonal populations expressed only the phenotype of morphological transformation, while 20% expressed all of the transformation phenotypes, including tumorigenicity, in addition to morphological transformation. The remaining clonal populations expressed varying combinations of one or more of the four transformation phenotypes. Clonal populations expressing almost all of the 16 possible combinations of the transformation phenotypes were observed, suggesting that the individual phenotypes segregated independently. Morphological transformation alone was a poor indicator of tumorigenicity, correctly predicting the tumorigenic potential of only 37% of the clonal populations. Among morphologically transformed clonal populations, coexpression of anchorage independence correctly predicted the tumorigenicity of 81% and coexpression of reconstruction of foci on a confluent lawn of wild-type cells correctly predicted the tumorigenicity of 91%. The probability that a morphologically transformed clonal population was tumorigenic correlated with the total number of transformation phenotypes expressed. Expression of the transformation phenotypes differed between tumorigenic and nontumorigenic clonal populations but not between clonal populations established from Type II and Type III foci. Tumorigenicity varied among transformed clonal populations that were induced by the different carcinogenic agents or were of spontaneous origin but did not differ between clonal populations established from Type II and Type III foci.
从自发产生或由致癌剂N-甲基-N'-硝基-N-亚硝基胍、苯并(a)芘二醇环氧化物-I和3-甲基胆蒽诱导产生的独立II型和III型病灶中建立了75个形态转化的10T1/2细胞克隆群体。对克隆群体进行了选定转化表型的表达特征分析，包括在增殖停止前生长至升高的饱和密度、锚定非依赖性、在野生型10T1/2细胞存在下接种时重建病灶的能力以及致瘤性。41%的克隆群体仅表达形态转化表型，而20%除形态转化外还表达所有转化表型，包括致瘤性。其余克隆群体表达四种转化表型中一种或多种的不同组合。观察到表达几乎所有16种可能转化表型组合的克隆群体，表明各个表型独立分离。仅形态转化是致瘤性的不良指标，仅正确预测了37%克隆群体的致瘤潜力。在形态转化的克隆群体中，锚定非依赖性的共表达正确预测了81%的致瘤性，在野生型细胞汇合草坪上重建病灶的共表达正确预测了91%的致瘤性。形态转化的克隆群体具有致瘤性的概率与所表达的转化表型总数相关。转化表型的表达在致瘤性和非致瘤性克隆群体之间存在差异，但在从II型和III型病灶建立的克隆群体之间没有差异。致瘤性在由不同致癌剂诱导产生或自发产生的转化克隆群体中有所不同，但在从II型和III型病灶建立的克隆群体之间没有差异。
