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Activation of mitogenic pathways and sensitization to estrogen-induced apoptosis: two independent characteristics of tamoxifen-resistant breast cancer cells?статья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 9 июня 2016 г.
- Авторы: Scherbakov A.M., Lobanova Y.S., Shatskaya V.A., Onopchenko O.V., Gershtein E.S., Krasil’nikov M.A.
- Журнал: Breast Cancer Research and Treatment
- Том: 100
- Номер: 1
- Год издания: 2006
- Издательство: Springer Nature
- Местоположение издательства: Switzerland
- Первая страница: 1
- Последняя страница: 11
- Аннотация: Paradoxical induction of apoptosis by estrogen has been described previously for estrogen-deprived and antiestrogen-resistant breast cancer cells. In this study we analyzed the possible interrelations between cell sensitization to estrogen apoptotic action and cell ability to (anti)estrogen-independent growth. Using tamoxifen-resistant sublines derived from the parent MCF-7 breast cancer cells by long-term tamoxifen treatment we demonstrated that resistant cells are characterized by increased level of EGF receptor and unexpected increase of VEGF receptor 2 (Flk-1/KDR) and its specific ligand, VEGF-A. The importance of the VEGF signaling in the autocrine regulation of cell growth was indicated by the ability of VEGF inhibitor, soluble fragment of Flt-1/Fc chimera, to suppress the phosphorylation of MAP kinases as well as to inhibit the estrogen-independent growth of MCF-7 cells. Sensitization of tamoxifen-resistant cells to estrogen-induced apoptosis required the additional continuous cultivation in steroid-depleted medium and did not depend on the activity of both EGF and VEGF pathways. Finally, we showed that treatment of the cells with 17beta-estradiol (10(-9) M) resulted in a marked increase in p53 level both in the resistant cells undergoing apoptosis and in the parent MCF-7 cells insensitive to apoptotic estrogen action. These data provide an important support for the existence of a disbalance between pro- and anti-apoptotic machinery in the resistant breast cancer cells that forms independently of the acquired ability to estrogen-independent growth.
- Добавил в систему: Щербаков Александр Михайлович