THE MDM-2 ONCOGENE IS TRANSLOCATED AND OVEREXPRESSED IN A MURINE PLASMACYTOMA CELL-LINE EXPRESSING WILD-TYPE P53

The cellular p53 protein has been demonstrated to possess growth-inhib itory activity. Recent work suggests that the murine double minute gen e (mdm-2) encodes a protein that may function as a cellular regulator or mediator of p53 function. We were interested in determining if the mdm-2 gene was overexpressed in mouse tumor cells, in particular mouse plasmacytomas that harbor wild type-p53 protein. A novel chromosomal translocation of the mdm-2 gene was detected in the SP2 cell line, tha t is derived from plasmacytoma MOPC21. The translocation results in a head-to-head arrangement of the mdm-2 gene (chromosome 10) with the im munoglobulin CK gene (chromosome 6), analogous to the translocations t hat activate the c-mye gene in murine plasmacytomas. Based on Northern blot analysis, the translocation induces a 10-fold elevation of mdm-2 RNA. Primer extension assays demonstrate that the 5' end of the mdm-2 RNA from the translocated gene is colinear with the 5' mdm-2 mRNA fro m an unrearranged gene, suggesting that the mRNA and encoded protein a re unaltered. This chromosomal translocation represents the first exam ple in which mdm-2 overexpression is activated by a genetic alteration other than gene amplification.