Malignant Properties of Sublines Selected from a Human Bladder Cancer Cell Line That Contains an Activated c-Ha-ras Oncogene1

The human bladder cancer cell line MGH-U1 (also designated 1-24 or EJ) contains an activated c-Ha-ros oncogene, which is amplified as compared to normal human fibroblasts. We have generated sublines from the MGH-U1 cell line: the MCH-U1/OCI subline was generated by dissociating spheroids formed from MGH-U1 cells; the I l-m/l-, and OCI-m/Fi were generated by in vivo passage of experimental lung métastasesformed after i.v. injection of MGH-U1 and MGH-U1/OCI lines into immune-deprived mice; the Ul/t subline was generated by in vivo passage of i.m. tumors formed from MGH-U1 cells. All sublines formed tumors in immune-deprived mice from smaller i.m. inocula than the parent line, and the I 1-ni/l , subline generated more spontaneous métastasesin lungs. Lung colony forming efficiency after i.v. injections of cells into similar mice was also greater for the sublines than for the parent MGH-U1 cells. The I l-rn/1 , and ()( I-in/1, were the most tumorigenic lines. Early passages of the MGH-U1/OCI subline showed the presence of double minute chromosomes, and amplification and increased expression of the c-Ha-ros oncogene as compared to the parental cell line. These changes were not present in later cultures of MGH-U1/OCI cells, and no consistent difference in the levels of gene amplification or expression between the parent line and the sublines was found. Thus the content and expression of the activated c-Ha-ros onco gene does not correlate with malignant properties of the sublines.