E.S. Gershtein, A.M. Scherbakov, A.A. Tuleuova, L.K. Ovchinnikova, N.E. Kushlinskii
Contemporary knowledge about the molecular mechanisms of breast cancer development and progression and its sensitivity or resistance to various drugs allows to proceed from standardized averaged therapy regimens to so called “personalized medicine”, i.e. to the prescription of treatment according to the individual patient’s features and biological characteristics of the tumor. One of the promising breast cancer molecular markers according to experimental data is polyfunctional nuclear transcription factor NF-B that plays an important role in cellular proliferation, apoptosis, inflammatory and autoimmune reactions by regulation of the expression of the genes involved in these processes.
The aim of this study was a comparative evaluation of NF-kB p65 and p50, its IkBα inhibitor, and upstream effector protein kinase Akt1 expression (total content) and/or activation state in human breast cancer and adjacent histologically unchanged mammary gland tissues in relation to receptor status and main clinico-pathologic factors. 119 breast cancer patients were enclosed in the study. Markers’ concentrations were measured by quantitative enzyme immunoassays using standard ELISA kits. It was demonstrated that in more than 90% of human breast cancers a coordinate increase of NF-kBp65 and p50 DNA-binding activities is observed. Total NF-kBp65, IkBa and effector protein kinase Akt1 concentrations are also increased. No significant associations between these markers and main breast cancer clinico-pathologic features including steroid receptors status were revealed, but the highest NF-kBp65 specific DNA-binding activity was found in the tumors with so called “triple receptor negative” receptor status that are resistant to both endocrine, and molecular targeted therapy. Hence, it is this specific group of patients that may benefit from the treatment with selective NF-kB inhibitors.
Significant and practically universal increase of NF-kB subunits and regulators expression and activities in breast cancer as compared to adjacent unchanged mammary gland tissue indicates to a possible independent role of these markers in the prognosis of the disease course in general and its sensitivity to certain types of therapy