[DR3/LARD mRNA spliced variants' frequency at colorectal cancer]

There are a lot of "death receptor" DR3/LARD mRNA variants that are formed during the alternative splicing. Membrane and soluble forms of the receptor are encoded with various types of the DR3/LARD mRNA and perform different functions. Using RT-PCR, the DR3/LARD mRNA spliced variants' frequency was measured in colon cancer patients' samples and cancer cell lines. In samples under investigation, four forms of the DR3/LARD mRNA were found with various frequencies. Two of them encoded the membrane receptors (LARD la mRNA and DR3beta mRNA) and other two expressed the soluble molecules (LARD 3 mRNA and soluble DR3beta mRNA). In blood of healthy volunteers 11 combinations (spectrums) of the DR3/LARD mRNA forms were revealed, and the "full" spectrum including all four variants of DR3/LARD mRNA dominated. In blood of colon cancer patients and tumour tissue samples, 6 DR3/LARD mRNA spectrums were found. The diversity of the DR3/LARD mRNA spectrums was decreased in colon cancer patients because of the frequency reduction of soluble DR3beta mRNA. Reduction of a variety of spectrums in cells of the patients was caused by decrease in occurrence of mRNA of the soluble DR3beta form. In samples of the tumor centers the spectrum with absence only mRNA of the soluble DR3beta form dominated. In blood of patients two spectrums prevailed: "full" range and presented mRNA LARD la and mRNA LARD 3. Only these two spectrums of mRNA DR3/LARD were also found in the tumor cell lines. Distinctions in occurrence of spectrums of DR3/LARD mRNA at healthy volunteers and colon cancer patients can define a different susceptibility of immunocompetent and tumor cells for apoptosis signals.