Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells.

We have investigated differences in gene expression between a metastatic and nonmetastatic clone of the DMBA-8 rat mammary adenocarcinoma cell line and have previously identified a differentially expressed gene WDNM1 (T.N. Dear, I.A. Ramshaw, and R.F. Kefford, Cancer Res., 48: 5203-5209, 1988). To further investigate differences in mRNA expression between these cell lines, a complementary DNA library from the nonmetastatic cell line was probed with labeled complementary DNA enriched for sequences specific to this line. We report here the identification in nonmetastatic cells of a second gene, WDNM2, which encodes a 1.7-kilobase mRNA corresponding to a protein (Mr 28,000-30,000) the expression of which shows a positive correlation with the nonmetastatic phenotype in three independently derived rat mammary adenocarcinoma cell lines and is regulated transcriptionally. Homologous sequences in the human genome have been identified. The function of this new gene may relate to regulation of the metastatic phenotype in this tumor.