The cellular p53
protein has been demonstrated to possess growth-inhibitory activity. Recent work suggests that the murine double minute gene (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, that is derived from
plasmacytoma MOPC21. The translocation results in a head-to-head arrangement of the mdm-2 gene (chromosome 10) with the
immunoglobulin C kappa gene (chromosome 6), analogous to the translocations that activate the c-myc 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 from an unrearranged gene, suggesting that the
mRNA and encoded
protein are unaltered. This
chromosomal translocation represents the first example in which mdm-2 overexpression is activated by a genetic alteration other than gene amplification.