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- W2610503334 abstract "Proc Amer Assoc Cancer Res, Volume 45, 20041726 At presentation 25-30% of human bladder tumours are classified as muscle–infiltrative, which by definition have already demonstrated the ability to invade & metastasise. Patients with these tumours have a significantly reduced 5-year survival rate, which often correlates with the development of metastatic disease following failure of treatment such as surgery or radiotherapy. Since metastasis is a multi-step process, in which the tumour cell must overcome many obstacles, it is likely that it involves the de-regulation of many genes. This complexity, combined with limitations of current animal models, means that bladder cancer metastasis is poorly understood. In an effort to further understand the metastatic process, we have established a metastatic variant of a non-metastatic rat bladder cell line. This was achieved by serial orthotopic implantation of the non-metastatic line into the bladder wall of immunocompetant animals. We have compared gene expression between the non-metastatic parent line and the metastatic variant using the Affymetrix rat 230A microarray. The results demonstrated that a total of 248 gene sequences differed by a factor of 2.5 or more between the two cell lines. Of these 248 sequences, 104 were known genes, with 55 being down-regulated in the metastatic cell line compared with the parental line and 49 being up-regulated. Furthermore, 33 of the 55 down-regulated known genes were absent altogether from the metastatic variant, while 22 of the 49 up-regulated known genes were present in the metastatic variant but absent from the parental line. Three classes of gene were strikingly well represented in the panel of differentially expressed genes; these encode proteins involved in (1) proteolysis (e.g. MMP3, MMP10, Cathepsin Y, cystatin N, TIMP3), (2) adhesion or cell-cell communication (e.g. connexins 30 and 40, various integrins) and (3) composition or stability of the extracellular matrix (e.g. fibronectin, decorin, lysyl oxidase, fibulin 3). Expression of candidate genes identified by the microarray experiment has been verified by RT-PCR and western blotting analysis; the pattern of differential protein expression is consistent with that of their mRNAs in the two variants. This model system may be suitable for identifying genes potentially involved in metastasis of bladder cancer and suggest novel targets for therapeutic intervention." @default.
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- W2610503334 date "2004-04-01" @default.
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- W2610503334 title "Identification of differentially expressed genes in a metastatic variant of an orthotopic model of bladder cancer" @default.
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