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Breast malignancies hold the lead in the pattern of cancers among women worldwide. Currently used methods for the instrumental diagnosis of breast cancer (BC) and their related diagnostic procedures are not sophisticated. The common constraint of instrumental techniques is the ambiguity of resultы interpretation that is associated with a diversity of individual characteristics of the structure and morphology of the breast. There is a need to search for novel diagnostic methods and oncomarkers, which are highly specific, highly sensitive, and inexpensive and able to reveal early stages in tumor development. In our opinion, a search for BC biomarkers is a promising and relevant area in oncology. Mass spectrometric methods are used to detect and identify proteomic markers in blood, biological fluids, tumor tissue, lysates, and secretomes of cancer cell lines. State-of-the-art high tech proteomics and mass spectrometric studies are oriented to the analysis of biological fluids and blood in order to identify new biomarkers. It is really that a blood test does not require any material obtained directly from tumor tissue and hence it is independent of the site of a tumor, implies the early detection of primary tumors or secondary foci, and is required by a medical oncologist in current clinical practice. The given review deals with the analysis of current methods to diagnose BC and to evaluate the efficiency of its therapy, by applying proteomic markers and the latest advances in clinical oncoproteomics.

The expression of СOX-2, VEGF, VEGFR-1, VEGFR-2, VEGFR-3, EGFR, endoglin (СD105), and IL-6 was analyzed in the human breast tumor cells having a varying metastatic potential. The role of these factors in the regulation of the metastatic potential of breast cancer cells, as well as that of COX-2 in the regulation of metastatic processes at the cellular level were examined. The potential capacity of human breast tumor cells to elaborate factors that stimulate tumor growth, angiogenesis, and metastasis was evaluated.

The proteome of lysates of the breast tumor cell lines MCF-7, BT-474, and ZR-75-1 was mapped, resulting in the sequence of 340 proteins. The proteins associated with the biosynthesis of PGE2 and with the regulation of cyclooxygenase-2 expression were identified and their relative expression levels were determined. Potential goals for the targeted therapy of breast cancer, such as prostaglandin E2 and D2 receptors, pros- taglandin E synthase, 15-hydroxyprostaglandin dehydrogenase and leukotriene-A4 -hydrolase, are of special interest in this group.

Mass spectrometric mapping of proteomic lysate of a MCF-7 cancer cell line was carried out, which identified 153 proteins having molecular weights of 5000 to 630000 Da, a high proportion of which was cytoplasmic and nuclear proteins. The latter accounted for 60 % of their total number whereas the proportion of extracellular and membrane proteins constituted 13 %. After using some selection criteria to analyze the findings, the authors present a list of 31 potential biomarkers and describe 12 promising breast anticancer therapeutic targets.

This paper analyzes 15-PGDH gene expression in the human breast cancer (BC) cell liness and describes the molecular principles through which the expression of the enzyme 15-PGDH is controlled in the tumor cells with a varying metastatic potential. There is an inverse correla- tion of 15-PGDH gene expression with COX-2 expression and the metastatic potential of tumor cells. Investigation of mechanisms for 15-PGDH regulation opens up new vistas and possibilities for the design of effective drugs for the targeted therapy of metastatic forms of BC.

The expression of the SMAD2, SMAD4, SMAD7, and СOX-2 genes and the levels of Smad4, phosphorylated Smad2, and Smad7 proteins were analyzed in the human breast cancer (BC) cell lines MCF-7, BT-474, and ZR-75-1. The SMAD2 and SMAD4 genes were found to suppress COX-2 gene expression in the estrogen receptor-positive BC cells and to be linked to their metastatic potential. Smad4 and Smad2 apparently suppress COX-2 mRNA and protein synthesis and Smad7 is their antagonist and stimulates COX-2 formation. Smad2, Smad4, Smad7 proteins may be regarded as new potential targets for targeted BC therapy.

Breast cancer (BC) is the most common form of cancer, leading to high mortality rates among women worldwide. In this study we have analyzed mRNA expression of 15-hydroxy-prostaglandin-dehydrogenases (15-HPGD), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and miRNAs (miR-21, miR-155) in three cell lines of estrogen-positive human breast carcinomas (MCF-7, BT-474, ZR-75-1). Results of three independent experiments have demonstrated significantly higher levels of COX-2 and COX-1 mRNAs in the cell line ZR-75-1 cells than in MCF-7 and BT-474 cells. mRNA levels of total 15-HPGD and functional-15-HPGD were lower in BT-474 than in MCF-7 and in ZR-75-1 cells. Synthesis of the 15-HPGD enzyme in BT-474 cells was blocked at the level of nuclear processing of an immature pre-mRNA. High expression of miR-21 was detected in all the tumor cell lines (MCF-7, ZR-75-1 and BT-474). In the breast cancer cell lines, the expression level of miR-155 was significantly lower than that of miR-21. Correlations have been found between dysregulation of miR-21, miR-155 and mRNA levels of 15-HPGD, COX-1, COX-2. The results obtained in this study showed that miR-21 and miR-155 regulate activity of several genes in the tumor cell and on some genes they exhibited a cumulative effect. Based on these results, we concluded that the miR-21 and miR-155 inhibit activity of the tumor suppressor gene 15-HPGD and induce a potential oncogene COX-2, which contributes to malignancy and metastasis of breast cancer cells. [ABSTRACT FROM AUTHOR]