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-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.
Berberich
S
S
Department of Biochemistry and Molecular Biology, Wright State University, Dayton, Ohio.
Cole
M
M
D000818:Animals; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics; D051379:Mice; D010954:Plasmacytoma / Q000235:genetics* / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D012334:RNA, Neoplasm; D016159:Tumor Suppressor Protein p53