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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...

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Autores principales: Strelnikov, Vladimir V., Kuznetsova, Ekaterina B., Tanas, Alexander S., Rudenko, Viktoria V., Kalinkin, Alexey I., Poddubskaya, Elena V., Kekeeva, Tatiana V., Chesnokova, Galina G., Trotsenko, Ivan D., Larin, Sergey S., Kutsev, Sergey I., Zaletaev, Dmitry V., Nemtsova, Marina V., Simonova, Olga A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838398/
https://www.ncbi.nlm.nih.gov/pubmed/33500458
http://dx.doi.org/10.1038/s41598-021-81851-y
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author Strelnikov, Vladimir V.
Kuznetsova, Ekaterina B.
Tanas, Alexander S.
Rudenko, Viktoria V.
Kalinkin, Alexey I.
Poddubskaya, Elena V.
Kekeeva, Tatiana V.
Chesnokova, Galina G.
Trotsenko, Ivan D.
Larin, Sergey S.
Kutsev, Sergey I.
Zaletaev, Dmitry V.
Nemtsova, Marina V.
Simonova, Olga A.
author_facet Strelnikov, Vladimir V.
Kuznetsova, Ekaterina B.
Tanas, Alexander S.
Rudenko, Viktoria V.
Kalinkin, Alexey I.
Poddubskaya, Elena V.
Kekeeva, Tatiana V.
Chesnokova, Galina G.
Trotsenko, Ivan D.
Larin, Sergey S.
Kutsev, Sergey I.
Zaletaev, Dmitry V.
Nemtsova, Marina V.
Simonova, Olga A.
author_sort Strelnikov, Vladimir V.
collection PubMed
description 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.
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spelling pubmed-78383982021-01-28 Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer Strelnikov, Vladimir V. Kuznetsova, Ekaterina B. Tanas, Alexander S. Rudenko, Viktoria V. Kalinkin, Alexey I. Poddubskaya, Elena V. Kekeeva, Tatiana V. Chesnokova, Galina G. Trotsenko, Ivan D. Larin, Sergey S. Kutsev, Sergey I. Zaletaev, Dmitry V. Nemtsova, Marina V. Simonova, Olga A. Sci Rep Article 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. Nature Publishing Group UK 2021-01-26 /pmc/articles/PMC7838398/ /pubmed/33500458 http://dx.doi.org/10.1038/s41598-021-81851-y Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Strelnikov, Vladimir V.
Kuznetsova, Ekaterina B.
Tanas, Alexander S.
Rudenko, Viktoria V.
Kalinkin, Alexey I.
Poddubskaya, Elena V.
Kekeeva, Tatiana V.
Chesnokova, Galina G.
Trotsenko, Ivan D.
Larin, Sergey S.
Kutsev, Sergey I.
Zaletaev, Dmitry V.
Nemtsova, Marina V.
Simonova, Olga A.
Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
title Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
title_full Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
title_fullStr Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
title_full_unstemmed Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
title_short Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
title_sort abnormal promoter dna hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7838398/
https://www.ncbi.nlm.nih.gov/pubmed/33500458
http://dx.doi.org/10.1038/s41598-021-81851-y
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