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

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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.