Heterogeneity of bladder cancer : relation to mutations of oncogenes and antioncogene

本研究旨在分析膀胱癌细胞系JMSU 1的异质性。通过有限稀释法从亲本JMSU 1中建立了8个克隆。这些克隆是异质性方面的以下properites：在相差显微镜下的体外形状，在体外倍增时间，在nu/nu小鼠的致瘤性，和侵袭活性。但是，在nu/nu小鼠中建立的皮下肿瘤的组织学显示克隆之间的组织学外观没有差异。指纹图谱分析表明，这些克隆来源于单细胞，没有污染。经PCR-SSCP和直接测序分析，所有克隆均存在p53基因第280位密码子（Arg*Thr）的点突变。Ha-ras和Ki-ras基因无突变。结论：本研究建立的克隆来源于同一细胞，但具有生物学异质性，可作为研究膀胱癌异质性的模型。

The present study was designed to analyze the heterogeneity of bladder cancer using the human bladder cancer cell line, JMSU1. Eight clones were established from the parental JMSU1 by the limiting dilution method. These clones were heterogeneous with respects to the following properites : in vitro shape under the phase-contrast microscope, in vitro doubling time, tumorigenicity in nu/nu mice, and invasion activity. But, histology of the subcutaneous tumors established in nu/nu mice demonstrated no difference in histological appearance among clones. Fingerprint analysis showed that these clones were derived from single cells and had no contamination. PCR-SSCP method followed by the direct sequencing revealed that all of the clones had the same point mutation at codon 280 (Arg*Thr) of p53 gene. However, there was no mutations in Ha-ras and Ki-ras genes. In conclusion, the clones established in the present study were derived from the same cell but showed the biological heterogeneity, and they would be useful as a model to study the heterogeneity of bladder cancer.