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The mdm2 oncogene encodes a 90-kilodalton nuclear phosphoprotein that binds and inactivates the p53 tumor suppressor protein. Here we report the observation of five alternatively spliced mdm2 gene transcripts in a range of human cancers and their absence in normal tissues. Transfection of NIH 3T3 cells with each of these forms gave foci of morphologically transformed cells. A higher frequency of splice variants lacking p53 binding domain sequences was found in late-stage and high-grade ovarian and bladder carcinomas. Four of the splice variants show loss of p53 binding, consistent with partial deletion of sequences encoding the p53 binding domain, but retain carboxyterminal zinc-finger domains. These observations suggest a reassessment of the transforming mechanisms of mdm2 and its relation to p53.

Type

Journal article

Journal

Nat Med

Publication Date

08/1996

Volume

2

Pages

912 - 917

Keywords

3T3 Cells, Alternative Splicing, Animals, Base Sequence, Cell Transformation, Neoplastic, DNA Primers, Disease Progression, Female, Humans, Leukemia, Mice, Molecular Sequence Data, Neoplasm Proteins, Nuclear Proteins, Ovarian Neoplasms, Protein Binding, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-mdm2, RNA, Transformation, Genetic, Tumor Suppressor Protein p53, Urinary Bladder Neoplasms