oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2020-19-4-138-145oncotomsk-1540Research ArticleОБЗОРЫREVIEWSРОЛЬ ЦИКЛИНА D1 В МЕХАНИЗМАХ РЕЗИСТЕНТНОСТИ К ГОРМОНАЛЬНОЙ ТЕРАПИИ ТАМОКСИФЕНОМROLE OF CYCLIN D1 IN THE MECHANISMS OF TAMOXIFEN RESISTANCEЭрдынееваД. Б.ErdyneevaD. B.

Эрдынеева Даяна Батоевна, студент 5 курса медико-биологического факультета

г. Томск, 634050, Московский тракт, 22

Daiana B. Erdyneeva, Student, Medical Biology Faculty

2. Moskovsky tract, 634050-Tomsk

daya-na@mail.ruhttps://orcid.org/0000-0002-0562-3878БабышкинаН. Н.BabyshkinaN. N.

Бабышкина Наталия Николаевна, кандидат медицинских наук, старший научный сотрудник лаборатории молекулярной онкологии и иммунологииSPIN-код: 2738-9275. Author ID (Scopus): 26641099700. Researcher ID (WOS): A-7526-2012.

г. Томск, 634009, пер. Кооперативный, 5;г. Томск, 634050, пр. Ленина, 36

Nataliya N. Babyshkina, PhD, Senior Researcher, Laboratory of Molecular Oncology and Immunology Author ID (Scopus): 26641099700. Researcher ID (WOS): A-7526-2012.

5, Kooperativny Street, 634009-Tomsk;36, Lenina Avenue, 634050-Tomsk

nbabyshkina@mail.ruhttps://orcid.org/0000-0003-3009-2404ДроноваТ. А.DronovaT. A.

Дронова Татьяна Анатольевна, аспирант института биологии; младший научный сотрудник лаборатории биологии опухолевой прогрессии. SPIN-код: 3516-2517. Author ID (Scopus): 6602971247. Researcher ID (WOS): R-5952-2016.

г. Томск, 634009, пер. Кооперативный, 5;г. Томск, 634050, пр. Ленина, 36

https://orcid.org/0000-0002-1195-4008ВторушинС. В.VtorushinS. V.

Вторушин Сергей Владимирович, доктор медицинских наук, профессор, заведующий отделением общей и молекулярной патологии. SPIN-код: 2442-4720. Author ID (Scopus): 26654562300. Researcher ID (WOS): S-3789-2016.

г. Томск, 634050, Московский тракт, 22;г. Томск, 634009, пер. Кооперативный, 5

Sergey V. Vtorushin, MD, DSc, Professor, Head of the Department of General and Molecular Pathology Author ID (Scopus): 26654562300. Researcher ID (WOS): S-3789-2016.

2. Moskovsky tract, 634050-Tomsk;5, Kooperativny Street, 634009-Tomsk

https://orcid.org/0000-0003-4382-5697СлонимскаяЕ. М.SlonimskayaE. M.

Слонимская Елена Михайловна, доктор медицинских наук, профессор, профессор кафедры онкологии медицинского факультета SPIN-код: 7763-6417. Author ID (Scopus): 6603658443. Researcher ID (WOS): C-7405-2012.

г. Санкт-Петербург, 199034, Университетская наб., 13Б

Elena M. Slonimskaya, MD, DSC, Professor of the Oncology Department Author ID (Scopus): 6603658443. Researcher ID (WOS): C-7405-2012.

13B, Universitetskaya Embankment, 199034-St-Petersburg

СтегнийВ. Н.StegniyV. N.

Стегний Владимир Николаевич, доктор биологических наук, профессор, заведующий лабораторией экологии генетики и охраны окружающей среды SPIN-код: 5588-5450. Author ID (Scopus): 57207471480. Researcher ID (WOS): N-7656-2014.

г. Томск, 634050, пр. Ленина, 36

Vladimir N. Stegniy, DSc, Professor, Head of the Department of Ecology, Genetics and Environmental Protection Author ID (Scopus): 57207471480. Researcher ID (WOS): N-7656-2014

36, Lenina Avenue, 634050-Tomsk

https://orcid.org/0000-0003-1526-9013ЧердынцеваН. В.CherdyntsevaN. V.

Чердынцева Надежда Викторовна, доктор биологических наук, профессор, член-корреспондент РАН, заведующая лабораторией молекулярной онкологии и иммунологии SPIN-код: 5344-0990. Author ID (Scopus): 6603911744. Researcher ID (WOS): C-7943-2012.

г. Томск, 634050, Московский тракт, 22;г. Томск, 634009, пер. Кооперативный, 5;г. Томск, 634050, пр. Ленина, 36

Nadejda V. Cherdyntseva, DSc, Corresponding Member of the Russian Academy of Sciences, Professor, Head of the Laboratory of Molecular Oncology and Immunology Author ID (Scopus): 6603911744. Researcher ID (WOS): C-7943-2012.

2. Moskovsky tract, 634050-Tomsk; 5, Kooperativny Street, 634009-Tomsk;36, Lenina Avenue, 634050-Tomsk

Сибирский государственный медицинский университет Министерства здравоохранения Российской ФедерацииРоссияSiberian State Medical UniversityRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; Национальный исследовательский Томский государственный университетРоссияCancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State UniversityRussian FederationСибирский государственный медицинский университет Министерства здравоохранения Российской Федерации; Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияSiberian State Medical University; Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of SciencesRussian FederationСанкт-Петербургский государственный университетРоссияSt. Petersburg UniversityRussian FederationНациональный исследовательский Томский государственный университетРоссияNational Research Tomsk State UniversityRussian FederationСибирский государственный медицинский университет Министерства здравоохранения Российской Федерации; Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; Национальный исследовательский Томский государственный университетРоссияSiberian State Medical University; Cancer Research Institute, Tomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State UniversityRussian Federation202001092020194138145Copyright © Эрдынеева Д.Б., Бабышкина Н.Н., Дронова Т.А., Вторушин С.В., Слонимская Е.М., Стегний В.Н., Чердынцева Н.В., 20202020Эрдынеева Д.Б., Бабышкина Н.Н., Дронова Т.А., Вторушин С.В., Слонимская Е.М., Стегний В.Н., Чердынцева Н.В.Erdyneeva D.B., Babyshkina N.N., Dronova T.A., Vtorushin S.V., Slonimskaya E.M., Stegniy V.N., Cherdyntseva N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/1540

Рецептор-позитивные опухоли составляют 65–70 % от всех случаев рака молочной железы (РМЖ). Наличие экспрессии эстрогеновых и прогестероновых рецепторов в качестве молекулярных мишеней опухоли обусловливает назначение гормональной терапии больным с рецептор-позитивным РМЖ. При проведении гормонотерапии препаратом выбора на протяжении последних десятилетий остается тамоксифен, являющийся селективным модулятором эстрогеновых рецепторов. Однако развитие резистентности является одной из основных причин, ограничивающих эффективность данного препарата. В связи с этим активно изучаются механизмы лекарственной устойчивости и ведется поиск прогностических маркеров клинического течения РМЖ и эффективности тамоксифена. Одним из таких молекулярных маркеров является представитель семейства регуляторных белков – циклин D1, которому отводится центральная роль в регуляции клеточного цикла. В обзоре представлены данные о вовлечении циклина D1 в эстроген-зависимый сигнальный каскад, охарактеризован ген CCND1 и его наиболее изученные полиморфные локусы, показана прогностическая значимость циклина D1 при рецептор-позитивном РМЖ. Проанализированы результаты экспериментальных и клинических исследований о взаимосвязи уровня экспрессии циклина D1 с эффективностью тамоксифена, рассмотрены современные подходы к преодолению гормонорезистентности на основе исследований циклина D1.

Hormone-receptor positive breast cancer is the most common molecular subtype and represents 60–75 % of all breast cancers (BC). The presence of specific molecular targets such as the estrogen/progesterone receptor determines the use of hormone therapy for patients with this subtype. Tamoxifen, a selective estrogen receptor modulator, remains the first adjuvant treatment choice for the hormone-receptor positive BC patients. However, tamoxifen resistance is the major limitation of its efficacy. In this regard, the study of drug resistance mechanisms as well as search for biological prognostic markers of tamoxifen efficacy is very important. Cyclin D1 is a representative of the regulatory protein family, which plays a central role in the cell cycle regulation. The data on the association between cyclin D1 and estrogen-dependent signaling as well as the characteristics of CCND1 gene and its most studied polymorphic loci, were presented. The prognostic significance of cyclin D1 in hormone-receptor positive BC receptor-positive breast cancer was described. The experimental and clinical studies data on the association between the cyclin D1 expression level and tamoxifen efficacy are analyzed. Current approaches to overcoming hormone resistance based on cyclin D1 studies were considered.

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The authors declare that there are no conflicts of interest present.