[The role of protein kinase PAK1 in the regulation of estrogen-independent growth of breast cancer].

The main goal of this work was to study the intracellular signaling pathways responsible for the development of hormone resistance and maintaining the autonomous growth of breast cancer cells. In particular, the role of PAK1 (p21-activated kinase 1), the key mitogenic signaling protein, in the development of cell resistance to estrogens was analyzed. In vitro studies were performed on cultured breast cancer cell lines: estrogen-dependent estrogen receptor (ER)-positive MCF-7 cells and estrogen-resistant ER-negative HBL-100 cells.

[The role of transcription factor Snail1 in the regulation of hormonal sensitivity of in vitro cultured breast cancer cells].

The loss of hormonal dependency in breast tumor cells is often accompanied by epithelial-mesenchymal transition (EMT) features and an increase in cell metastasizing and invasiveness. Here we studied the role of transcription factors Snail1--the central mediator of EMT, in the progression of hormonal resistance of breast cancer cells. The experiments were performed on the estrogen receptor(ER)-positive estrogen-dependent MCF-7 breast cancer cells, ER-positive estrogen-resistant MCF-7/LS subline generated through long-term cultivation of the parental cells in steroid-free medium, and ER-negative estrogen-resistant HBL-100 breast cancer cells.

[The molecular mechanism responsible for the adaptation of malignant tumors to hormonal drugs: a role of phophatidylinositol-3-kinase and phosphoinositide-dependent proteins].

Phophatidylinositol-3-kinase (PI3K) is a major intracellular protein that is responsible for the transmission of an antiapoptotic signal and controls the survival of tumor cells upon exposure to damaging agents. Experiments using different tumor cell cultures have shown that the resistance of cells to the antiproliferative action of dexamethasone, caused by their long cultivation with the hormone, is associated with the activation of PI3K and the transcription factor STATS. The activation of PI3K and STAT3 in the dexamethasone-resistant cells correlates with the increase in the total thyrosine kinase activity and with the decrease in the sensitivity of cells to exogenous proliferative agents, such as 17beta-estradiol.

[Role of phosphatidylinositol signalling path in developing hormonal resistance in tumor cells].

Phosphatidylinositol 3-kinase (PI3K) is a key regulatory protein which is responsible for anti-apoptotic signal transduction regulating cell survival during exposure to damaging factors. The report deals with the role of the PI3K signaling pathway in regulating cellular response to hormones and, particularly, in development of resistance as a result of long-term exposure of cells to steroid cytostatic hormones. In our study, even a short-term exposure of transformed fibroblasts of hamster (line 2PK) resulted in an activation of main PI3K effectors (MAP-kinase and protein kinase B (PKB)) which appeared against the background of hormone-induced inhibition of cellular growth.