Endocrine Abstracts

Type 1 deiodinase (D1) catalyses deiodination of tyroxine (T4), which leads either to synthesis of triiodothyronine or reverse triiodothyronine (rT3). T3 can influence the process of neoplasia through its receptors which act as transcription factors and regulate the expression of many tumor suppressor genes and oncogenes. The aim of the study was to analyze the changes in expression of alternatively spliced variants of D1 mRNA in clear cell Renal Cell Carcinoma (ccRCC), which is the most common type of renal cancers (75% of primary renal malignancies). Tissue samples were obtained with the permission of the local Ethical Committee of Human Studies. Using quantitive real-time PCR we have analyzed: 33 samples of ccRCC with their controls (the contralateral pole of the same kidney not infiltrated by cancer, assigned C) as well as control samples from patients suffering from other, nonneoplastic kidney abnormalities (6 samples, assigned N). The expression of the whole pool of D1 transcript variants was dramatically lowered in ccRCC tissues. The separately performed expression analysis of alternatively spliced D1 transcript variants, which differ in the presence or absence of subexon 1b, also exhibited about 90% decrease of mRNA in both transcript variants of cancer tissues. Simultaneously, the comparison of these alternatively spliced mRNA groups revealed that ratio: (whole pool of D1 transcripts)/(transcripts containing the1b exon) as well as relation: (whole pool of D1 transcripts)/(transcripts devoid of the1b exon) were increased several times in the ccRCC in comparison with controls. This observation suggests the existence of at least one another alternatively spliced variant, which extends the whole poll of D1 transcripts and possibly is overexpressed in ccRCC. Our results indicated that the alternative splicing process of deiodinase type I can be disturbed in ccRCC.