Aleksandrova N. Metabolism of polyamines and their relationship with functioning of nuclear transcription factor NF-kappaB in breast tumors

The work is devoted to study of relationship between metabolism of polyamines (PA) and function of nuclear transcription factor NF-kappaB. The indices of PA metabolism in the patients with breast tumors are studied. In model experiments performed by biosensor and fluorimetric techniques, it is demonstrated that the natural PA, in contrast to a synthetic analogue of PA and an inhibitor of biosynthesis of polyamines - difluoromethylornithine (DFMO), facilitaes the binding of p50 to specific DNA sequences. It is shown that in mouse breast carcinoma cells Ca 755, rat carcinosarcoma cells Walker-256 and human breast cancer cells MCF-7, DFMO-induced polyamines depletion causes an increase of the content of p50 and, to a lesser extent, p65 subunits of NF-kappaB in the nuclei. If the DFMO-induced polyamines depletion is compensated by adding putrescine, the effect of PA depletion on the content of p50 and p65 is fully supressed. It is found that polyamines depletion causes a decrease of the content of the protein products of the oncogenes c-myc and bcl-XL, thus indicating that NF-kappaB is unable to perform its transcriptional function with respect to the studied genes under conditions of DFMO-induced polyamines depletion.