medgenМедицинская генетикаMedical Genetics2073-7998Publishing House «Genius Media» LLCmedgen-226Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHИсследование однонуклеотидных полиморфизмов генов ABC-транспортеров в опухоли молочной железы: связь с экспрессиейThe study single nucleotide polymorphisms ABC-transporter genes in breast cancer: correlation with expressionЦыгановМ. М.TsyganovM. M.TsyganovMM@yandex.ruИбрагимоваМ. К.IbragimovaM. K.noemail@neicon.ruДерюшеваИ. В.DeryushevaI. V.noemail@neicon.ruЛитвяковН. В.LitviakovN. V.noemail@neicon.ruТомский национальный исследовательский медицинский центр Российской академии наук; Национальный исследовательский Томский государственный университетРоссияTomsk National Research Medical Center Russian Academy of Sciences; Tomsk State UniversityRussian FederationТомский национальный исследовательский медицинский центр Российской академии наукРоссияTomsk National Research Medical Center Russian Academy of SciencesRussian Federation2017180420171612530Copyright © Цыганов М.М., Ибрагимова М.К., Дерюшева И.В., Литвяков Н.В., 20172017Цыганов М.М., Ибрагимова М.К., Дерюшева И.В., Литвяков Н.В.Tsyganov M.M., Ibragimova M.K., Deryusheva I.V., Litviakov 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.medgen-journal.ru/jour/article/view/226

Наши предыдущие исследования показали, что изменение экспрессии генов ABC-транспортеров ( ABCB1 , ABCB3 , ABCC1 , ABCC2 , ABCC5 , ABCG1 , ABCG2 ) связано с эффективностью неоадъювантной химиотерапии. Тем не менее, механизмы регуляции экспрессии данных генов химиорезистентности остаются неясным. Как полагают многие исследователи, в данный процесс могут быть вовлечены однонуклеотидные полиморфизмы. Материалы и методы. Основываясь на этом, было проведено микроматричное исследование полиморфизмов в генах ABC-транспортерах. Всего в исследование было включено 84 пациента с раком молочной железы. В качестве исследуемого материала были использованы биопсийные опухолевые образцы до лечения и операционные после химиотерапии. Оценку экспрессии генов проводили методом ПЦР в режиме реального времени. Результаты. Было проанализировано 195 полиморфизмов 7 генов множественной лекарственной устойчивости. Было установлено 8 полиморфизмов, а именно, ABCB1 rs2235035 , ABCB3 rs241430 , ABCB3 rs241429 , ABCC1 rs17205838 , ABCC1 rs35596 , ABCC2 rs4919395 , ABCC2 rs2756103 и ABCG2 rs59409230 , которые участвуют в регуляции экспрессии собственных генов. Выводы. Таким образом, в нашем исследовании были установлены новые SNP оказывающие влияние на экспрессию генов ABC-транспортеров, что может дать дополнительные сведения о механизмах регуляции экспрессии генов ABC и формировании химиорезистентности.

Our previous research establishes that changes of expression of the ATP-binding cassette genes family ( ABCB1 , ABCB3 , ABCC1 , ABCC2 , ABCC5 , ABCG1 , ABCG2 ) is connected with the neoadjuvant chemotherapy effect. However, the mechanism of regulation of resistance gene expression remains unclear. As many researchers believe, single nucleotide polymorphisms can be involved in this process. Materials and methods. Thereupon, microarray analysis is used to study polymorphisms in ATP-binding cassette genes. The study group 84 patients with breast cancer. The test material as tumor biopsy samples were used to treat and operation after chemotherapy. The evaluation of genes expression was performed by real time PCR. Results. Total 195 single nucleotide polymorphisms 7 gene family of ABC-transporters have been analyzed. It is thus found that MDR gene expression is connected with 8 polymorphisms, i.e. ABCB1 rs2235035 , ABCB3 rs241430 , ABCB3 rs241429 , ABCC1 rs17205838 , ABCC1 rs35596 , ABCC2 rs4919395 , ABCC2 rs2756103 and ABCG2 rs59409230 which participate in the regulation of expression of own genes. Conclusions. Therefore, this work shows that the majority of mutations and polymorphisms of ABC genes have a substantial impact on the ATP-binding cassette transporter regulation, it can give more information about the mechanisms of ABC regulation of gene expression and the formation of chemoresistance.

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