IN VITRO- and IN VIVO- experimental models for balanced activity of oncogenes and tumor-suppressor genes in normal and malignant cells

Abstract


Iskra Ventseslavova Sainova*, Ilina Vavrek, Velichka Pavlova, Ivan Iliev, Lilija Yossifova, Elena Gardeva, Elena Nikolova, Teodora Daneva, Roberto Nitsch and Anna Nitsch

Gene transfer in laboratory-cultivated mouse embryonic stem cells (mESCs) was made by appropriate recombinant DNA-constructs. Electrophorhetic profiles of genetic material from wild type (WT) on oncogene DCN1 and “knock-down” (KD) on it inbred lines of experimental mice differed not only on it, but also on the tumorsuppressor gene HACE1 between both categories of laboratory rodents. The results obtained were compared with previous data, received from malignant rat insulinoma RIN-5F cells, transfected by recombinant gene constructs with inserted copy of secretagogin gene, by their IN VITRO-co-cultivation with malignant cell precursors, derived from populations of non-transfected laboratory-cultivated mESCs in the presence of doxyciclin, probably by activation of tumor-suppressor genes of STAT-family. These data were confirmed by the differences noticed in the degree of myeloid differentiation of derived precursor cells in their IN VITRO-co-cultivation with containing additional copy of secretagogin gene Rin-5F malignant rat insulinoma cells, in comparison with the results, obtained in their laboratory co-cultivation with non-treated human cervical carcinoma Hela cells, as well as with derived normal mESCs, containing additional copy of the oncogene DCN1 as a result of their transfection with recombinant DNAconstructs. On the other hand, the derived normal cells with inserted additional copy of oncogene indicated safety, immunogenity, and they also indicated preserved normal cell characteristics.

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