Re: T. Neil Dear et al., Transcriptional down-regulation of a rat gene, WDNM2, in metastatic DMBA-8 cells. Cancer Res., 49: 5323-5328, 1989.
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9,10-Dimethyl-1,2-benzanthracene↗
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T N Dear
Publications and source records attributed to T N Dear.
Molecular oncogenetics of metastasis.
Metastasis is a complex non-stochastic process that is most likely the result of genetic and epigenetic interactions of a wide variety of genes. The search for a single gene which can encompass such a pleiotropic response as to account for the observed phenotypic characteristics of metastatic tumour populations has been unsuccessful. Particular studies involving gene transfection, subtractive hybridisation and cell fusion are beginning to identify specific genes which contribute to metastasis in some cell types. However, such analyses are complicated by the inherent genetic instability and phenotypic heterogeneity present in tumour populations. A more detailed understanding of the metastatic process may require an abandoning of current generalised approaches to metastasis in favour of concentrating on key components of the metastatic cascade such as adhesion and invasion.
Adenovirus Early Proteins↗
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.
9,10-Dimethyl-1,2-benzanthracene↗
Differential expression of a novel gene, WDNM1, in nonmetastatic rat mammary adenocarcinoma cells.
Subtractive hybridization was used to investigate differences in gene expression between a metastatic clone and nonmetastatic clone of the rat mammary adenocarcinoma line DMBA-8 which differ 100-fold in their metastatic behavior. Several differentially expressed highly homologous mRNAs (600 to 900 base pairs) were identified from the nonmetastatic line which are expressed at a level 20-fold higher than in the metastatic clone. Available sequence data show no homology to published gene sequences. There is no difference between the metastatic and nonmetastatic clones regarding DNA restriction fragment sizes or copy number of the gene. Expression of this newly described gene, named WDNM1, may be an important correlate of nonmetastasis in this tumor model.
9,10-Dimethyl-1,2-benzanthracene↗