Molecular Basis of Carcinogenesis of Aguired Cystic Disease of the Kidney

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Recently, it is becoming a serious problem that patients with long term hemodialysis frequently develop aquired cystic disease of the kidney (ACDK), which presents a high rate of complication with renal cell carcinoma. In order to elucidate the mechamism by which renal cell cancer occurs in ACDK,we tried to establish a model of renal cell tumor derived from diphenyl thiazole (DPT) -induced polycystic kidney disease (PKD) in rats. In addition, we tried to analyze the early changes at molecular level during DPT-induced renal cyst formation to reveal the gene expressions specific to DPT-induction. For the former purpose, we administered N-nitrosomorpholine (NNM) known as a powerful carcinogenic substance to the rats with DPT-induced PKD and observed the neoplastic lesions derived from epithelium of cysts in two of 10 kidneys. For the latter purpose, we examined the structural change of extracellular matrix by immunohistochemical analysis of laminin, collagen type III and IV and chased the genes expressing specifically to the early phase of DPT-induced cyst formation by the run-on transcription and the RNA differential display analysis. As a result, we observed the expression of several genes including c-myc, c-fos and c-erbB_2 decreased the early days after administration of DPT.In addition, we obtained four candidates of those genes and determined the partial cDNA sequences of two candidates, which were not identical to any cDNA sequence already determined. From now on, we are goning to identify other genes expressing specifically to DPT-induction and next to search NNM-specific genes.