Introduction of normal chromosome 3p modulates the tumorigenicity of a human renal cell carcinoma cell line YCR.
Introduction of normal chromosome 3p modulates the tumorigenicity of a human renal cell carcinoma cell line YCR.
复制标题
正常染色体 3p 的引入调节人肾细胞癌细胞系 YCR 的致瘤性。
作者：
M. Shimizu;J. Yokota;N. Mori;T. Shuin;M. Shinoda;M. Terada;M. Oshimura
有人认为，3号染色体短臂(3p)上的一个或多个基因的缺失和/或突变失活可能在人肾细胞癌(RCC)的发生发展中起重要作用。如果它是正确的，正常等位基因可能携带肿瘤相关表型的抑制活性(S)。为了验证这一假设，我们通过微细胞融合将含有3P的单个染色体导入人肾癌细胞系YCR，并检测了其在裸鼠体内的致瘤性和体外生长特性。将来自正常人成纤维细胞的以下染色体转移到YCR或6-硫鸟嘌呤抗性的YCR细胞中：T(X；3)由Xpter值大于Xq26：：3p12大于3pter值组成，X，pSV2neo标记的11号染色体，以及3/t由pSV2neo标记的3p和未知片段组成。T(X；3)或3/t的引入抑制了细胞的成瘤性或调节了肿瘤的生长速度，而其他染色体，即X和11的转移对细胞的成瘤性或肿瘤生长速度没有影响。体外生长特性，即细胞在含1%或10%血清的培养液中的生长，在软琼脂中的生长和饱和密度，与肿瘤的生长无关。此外，失去t(X；3)的6-硫代鸟嘌呤耐药分离物的肿瘤生长速度与亲本YCR细胞相似。因此，3P的引入至少调节了肿瘤的生长，表明3P上存在一个可能的人肾细胞癌抑癌基因(S)。
It has been suggested that loss and/or mutational inactivation of a gene or genes on the short arm of chromosome 3 (3p) may play a crucial role in the development of human renal cell carcinoma (RCC). If it is correct, the normal allele may carry suppressor activity for a tumor-associated phenotype(s). In order to test the hypothesis, we introduced a single chromosome containing 3p into a human renal cell carcinoma cell line YCR via microcell fusion, and examined tumorigenicity in nude mice and in vitro growth-properties. The following chromosomes derived from normal human fibroblasts were transferred to YCR or 6-thioguanine-resistant YCR cells: t(X;3) consisting of Xpter greater than Xq26::3p12 greater than 3pter, X, pSV2neo-tagged chromosome 11, and 3/t consisting of pSV2neo-tagged 3p and unknown segments. The introduction of t(X;3) or 3/t resulted in suppression of tumorigenicity or modulation of tumor-growth rate, whereas transfer of other chromosomes, i.e., X and 11, had no effect on tumorigenicity or tumor-growth rate of the cells. In vitro growth properties, i.e., cell-growth in medium containing 1% or 10% serum, growth in soft-agar and saturation density, were not correlated with the tumor-growth. In addition, the tumor-growth rate of 6-thioguanine-resistant segregants which have lost the t(X;3) became similar to that of the parental YCR cells. Thus, the introduction of 3p modulated at least the tumor-growth, indicating the presence on the 3p of a putative tumor-suppressor gene(s) for human RCC.