The relationships between snail1 and estrogen receptor signaling in breast cancer cells

Abstract

The loss of hormonal dependency of breast tumor cells is often accompanied with the appearance of epithelial-mesenchymal transition (EMT) features and increase in cell metastasis and invasiveness. The central role in the EMT belongs to transcription factors Snail responded for the decrease in E-cadherin expression and cell contacts, stimulation of cell mobility and invasiveness. Aim was to study the relationships between estrogen receptor machinery and Snail1 signaling, and mechanism of Snail1 regulation in hormone-resistant breast cancer cells. The experiments were performed on the estrogen-dependent MCF-7 breast cancer cells, estrogen-hyposensitive MCF-7/LS subline generated through long-term cultivation of the parental cells in steroid-free medium, and ER-negative estrogen-resistant HBL-100 cells. Snail1, estrogen receptor, p65 NF-κB, E-cadherin levels were analyzed by Western blot. We found that decrease in the estrogen dependency is correlated with increase in Snail1 expression and activity, we demonstrated the Snail1 involvement in the negative regulation of ER, and showed that Snail1 inhibition partially restores the sensitivity of the estrogen-hyposensitive cells to antiestrogen tamoxifen. Furthermore, NF-κB was found to serve as a positive regulator of Snail1 in breast cancer cells, and simultaneous inhibition of NF-κB and Snail1 resulted in additional increase in cell response to tamoxifen. In general, the results obtained demonstrate the phenomenon of Snail1 activation in the hormone-resistant breast cancer cells, and show that Snail1 and NF-κB may serve as an important targets in the treatment of breast cancer, both estrogen-dependent and estrogen-independent tumors.

PCP4/PEP19 promotes migration, invasion and adhesion in human breast cancer MCF-7 and T47D cells

“…Many studies have linked EMT to the invasive and metastatic potential of breast cancer cells [25, 26]. A feature of EMT is suppression of E-cadherin expression, which disrupts cell-cell adhesion and activates signaling pathways that control cell migration, invasion, and metastasis [27, 28]. Bmi-1 is an upstream regulator of Snail expression, which in turn promotes the EMT via suppression of E-cadherin and upregulation of vimentin expression [29, 30].…”

Exosomes and development of cancer cell resistance to metformin: pilot study

“…Целый ряд клинико-эпидемиологических исследо-ваний показал, что этот препарат существенно сни-жает риск развития онкологических заболеваний и проявляет высокую противоопухолевую актив-ность как in vivo, так и in vitro [1,2]. Более того, изучение механизма действия бигуанидов проде-монстрировало, что их антипролиферативная ак-тивность реализуется как минимум частично, через активацию аденозинмонофосфат-активируемой протеинкиназы (adenosine monophosphate-activated protein kinase, АМРК) и АМРК-зависимое подав-ление сигналинга mTOR (мишень рапамицина в клетках млекопитающих) [3,4].…”

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

“…В пользу этого предположения свидетельствовали продемонстрированный нами ранее низкий уровень Snail1 в клетках MCF-7 [18], а также известные данные о способности ER подавлять активность Snail1 (через активацию специфического белка-супрессора Snail1 МТА3) [19,20].…”