Introduction of normal chromosome 3p modulates the tumorigenicity of a human renal cell carcinoma cell line YCR.
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.
Shimizu
M
M
Laboratory of Cytogenetics, Kanagawa Cancer Center Research Institute, Yokohama, Japan.
Yokota
J
J
Mori
N
N
Shuin
T
T
Shinoda
M
M
Terada
M
M
Oshimura
M
M
D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D012150:Polymorphism, Restriction Fragment Length; D013489:Suppression, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured