Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer

Cell transmembrane receptors and extracellular matrix components play a pivotal role in regulating cell activity and providing for the concerted integration of cells in the tissue structures. We have assessed DNA methylation in the promoter regions of eight integrin genes, two nidogen genes, and the dystroglycan gene in normal breast tissues and breast carcinomas (BC). The protein products of these genes interact with the basement membrane proteins LAMA1, LAMA2, and LAMB1; abnormal hypermethylation of the LAMA1, LAMA2, and LAMB1 promoters in BC has been described in our previous publications. In the present study, the frequencies of abnormal promoter hypermethylation in BC were 13% for ITGA1, 31% for ITGA4, 4% for ITGA7, 39% for ITGA9, 38% for NID1, and 41% for NID2. ITGA2, ITGA3, ITGA6, ITGB1, and DAG1 promoters were nonmethylated in normal and BC samples. ITGA4, ITGA9, and NID1 promoter hypermethylation was associated with the HER2 positive tumors, and promoter hypermethylation of ITGA1, ITGA9, NID1 and NID2 was associated with a genome-wide CpG island hypermethylated BC subtype. Given that ITGA4 is not expressed in normal breast, one might suggest that its abnormal promoter hypermethylation in cancer is non-functional and is thus merely a passenger epimutation. Yet, this assumption is not supported by our finding that it is not associated with a hypermethylated BC subtype. ITGA4 acquires expression in a subset of breast carcinomas, and methylation of its promoter may be preventive against expression in some tumors. Strong association of abnormal ITGA4 hypermethylation with the HER2 positive tumors (p = 0.0025) suggests that simultaneous presence of both HER2 and integrin α4 receptors is not beneficial for tumor cells. This may imply HER2 and integrin α4 signaling pathways interactions that are yet to be discovered. © 2021, The Author(s).

Авторы
Strelnikov V.V.1 , Kuznetsova E.B.1, 3 , Tanas A.S.1 , Rudenko V.V.2 , Kalinkin A.I.1 , Poddubskaya E.V.4, 5 , Kekeeva T.V.1 , Chesnokova G.G.1 , Trotsenko I.D. 6 , Larin S.S.7, 8 , Kutsev S.I.1 , Zaletaev D.V.1, 3 , Nemtsova M.V.1, 3 , Simonova O.A.2
Журнал
Издательство
Nature Publishing Group
Номер выпуска
1
Язык
Английский
Статус
Опубликовано
Номер
2264
Том
11
Год
2021
Организации
  • 1 Epigenetics Laboratory, Research Centre for Medical Genetics, Moskvorechie St 1, Moscow, 115522, Russian Federation
  • 2 Molecular Genetic Diagnostics Laboratory 2, Research Centre for Medical Genetics, Moskvorechie St 1, Moscow, 115522, Russian Federation
  • 3 Medical Genetics Laboratory, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St 8-2, Moscow, 119991, Russian Federation
  • 4 Clinic of Personalized Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Trubetskaya St 8-2, Moscow, 119991, Russian Federation
  • 5 VitaMed LLC, Seslavinskaya St 10, Moscow, 121309, Russian Federation
  • 6 Institute of Medicine, Peoples’ Friendship University of Russia (RUDN University), Miklukho-Maklaya St 6, Moscow, 117198, Russian Federation
  • 7 Molecular Immunology Laboratory, Federal Scientific Clinical Centre of Pediatric Hematology Oncology Immunology Named After Dmitry Rogachev, Samory Mashela St 1, Moscow, 117997, Russian Federation
  • 8 Gene Therapy Laboratory, Institute of Gene Biology, Vavilova St 34/5, Moscow, 119334, Russian Federation
Дата создания
20.04.2021
Дата изменения
20.04.2021
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/71905/
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