ACTIVATION OF MECHANISMS, MEDIATED BY DCN1-HACE1-, JAK-STAT- AND NF-ΚB- CASCADE REGULATORY PATHWAYS IN IN VITRO- AND IN VIVO-EXPERIMENTAL MODELS

International Journal of Innovations in Biological and Chemical Sciences, Vol. 6, 2015, 48-59

Iskra Sainova, Ilina Valkova, Bistra Alexieva, Iliana Ilieva, Elena Nikolova

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ABSTRACT

Mechanisms for activation of normal cell differentiation, with suppression of malignant cell transformation, at the same time, by development of ways for safe application, were searched and studied. In this connection, role of components from Dcn1-HACE1-, JAK-STAT-, and NF-κB-mediated cascade regulatory pathways in these processes, was particularly investigated. Additional oncogene copy was inserted into normal mouse ESCs, for eventual elongation of life, it was important preserved normal/non-malignant characteristics to be tested and proved. On the other hand, additional tumor-suppressor gene copy was inserted into malignant cells, for eventual decrease of their malignant potential. After propagation of fibroblasts from 3T3 cell line, derived from Balb/c mouse embryos, one part of them was pre-cultivated in cultural fluid, in which mouse malignant myeloma cells were previously cultivated, for a period of 2-3 days. After freezing of separate sub-populations from the so incubated cells for 2-4 weeks in the presence of cryo-protector Dymethylsulfoxide (DMSO), subsequent thawing and re-incubation, osteoclast-like characteristics were assessed. When the cultural fluid from the so-derived osteoclast-like cells was added to de novo-received confluent monolayer of 3T3 cells, signs of osteoblast lineage differentiation were noted. In co-cultivation of the so derived from mouse embryonic progenitors osteoblast-like and osteoclast-like cells, zones of destroyed osteoblast-like cell monolayer could be noted.

Keywords Cell differentiation direction, Cell progenitors, Cascade regulatory mechanisms, Extra-cellular matrix components, Organic detergents