In vitro- and in vivo- experimental models for balanced activity of oncogenes and tumor-suppressor genes in normal and malignant cells

Abstract

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 tumor-suppressor 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 ofSTAT-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 oncogeneDcn1 as a result of their transfection with recombinant DNA-constructs. 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. Key words: Oncogenes, tumor-suppressor genes, myeloid cell precursors, recombinant gene constructs, cell transfection.