Albino A P, Sozzi G, Nanus D M, Jhanwar S C, Houghton A N
Memorial-Sloan Kettering Cancer Center, New York, New York 10021.
Oncogene. 1992 Nov;7(11):2315-21.
Human melanoma provides a model to study malignant transformation and tumor progression. Expression of ras oncogenes in cultured normal human diploid melanocytes has induced a subset of phenotypic traits that are characteristic of malignant melanoma cells, including altered morphology, anchorage independence, induction of class II MHC antigens, up-regulation of the ganglioside GD3, and chromosomal abnormalities. However, other characteristics of melanoma, such as loss of expression of adenosine deaminase-binding protein and tumorigenicity, were not observed. We report here that melanocytes infected with a retrovirus containing the viral Ha-ras oncogene underwent complete transformation, acquiring all phenotypic characteristics of malignant melanomas observed in vivo. Transformation occurred in a sequential manner and was associated with spontaneous chromosomal instability. Cytogenetic analysis of transformed melanocytes indicated that the earliest structural chromosomal abnormalities were isochromosomes 6p and 9q followed by complete loss of chromosome 1p, all common karyotypic abnormalities described in human melanomas. The findings suggest that these chromosome regions which are deleted or relatively deficient may contain genes that are critical for the initiation and progression of the melanoma phenotype.
人类黑色素瘤为研究恶性转化和肿瘤进展提供了一个模型。在培养的正常人二倍体黑色素细胞中，ras癌基因的表达诱导了一部分恶性黑色素瘤细胞所特有的表型特征，包括形态改变、不依赖贴壁生长、II类主要组织相容性复合体抗原的诱导、神经节苷脂GD3的上调以及染色体异常。然而，并未观察到黑色素瘤的其他特征，如腺苷脱氨酶结合蛋白表达缺失和致瘤性。我们在此报告，感染含有病毒Ha-ras癌基因的逆转录病毒的黑色素细胞发生了完全转化，获得了在体内观察到的恶性黑色素瘤的所有表型特征。转化以一种连续的方式发生，并与自发的染色体不稳定性相关。对转化后的黑色素细胞进行的细胞遗传学分析表明，最早的结构性染色体异常是6号染色体短臂等臂染色体和9号染色体长臂等臂染色体，随后是1号染色体短臂的完全缺失，这些都是人类黑色素瘤中描述的常见核型异常。这些发现表明，这些被缺失或相对缺乏的染色体区域可能包含对黑色素瘤表型的起始和进展至关重要的基因。
