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

Abstract 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...

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Autores principales:	Vladimir V. Strelnikov, Ekaterina B. Kuznetsova, Alexander S. Tanas, Viktoria V. Rudenko, Alexey I. Kalinkin, Elena V. Poddubskaya, Tatiana V. Kekeeva, Galina G. Chesnokova, Ivan D. Trotsenko, Sergey S. Larin, Sergey I. Kutsev, Dmitry V. Zaletaev, Marina V. Nemtsova, Olga A. Simonova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9674b2bcc0154773b10c7499d5ce84fc
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spelling	oai:doaj.org-article:9674b2bcc0154773b10c7499d5ce84fc2021-12-02T13:24:25ZAbnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer10.1038/s41598-021-81851-y2045-2322https://doaj.org/article/9674b2bcc0154773b10c7499d5ce84fc2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-81851-yhttps://doaj.org/toc/2045-2322Abstract 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.Vladimir V. StrelnikovEkaterina B. KuznetsovaAlexander S. TanasViktoria V. RudenkoAlexey I. KalinkinElena V. PoddubskayaTatiana V. KekeevaGalina G. ChesnokovaIvan D. TrotsenkoSergey S. LarinSergey I. KutsevDmitry V. ZaletaevMarina V. NemtsovaOlga A. SimonovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Vladimir V. Strelnikov Ekaterina B. Kuznetsova Alexander S. Tanas Viktoria V. Rudenko Alexey I. Kalinkin Elena V. Poddubskaya Tatiana V. Kekeeva Galina G. Chesnokova Ivan D. Trotsenko Sergey S. Larin Sergey I. Kutsev Dmitry V. Zaletaev Marina V. Nemtsova Olga A. Simonova Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
description	Abstract 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.
format	article
author	Vladimir V. Strelnikov Ekaterina B. Kuznetsova Alexander S. Tanas Viktoria V. Rudenko Alexey I. Kalinkin Elena V. Poddubskaya Tatiana V. Kekeeva Galina G. Chesnokova Ivan D. Trotsenko Sergey S. Larin Sergey I. Kutsev Dmitry V. Zaletaev Marina V. Nemtsova Olga A. Simonova
author_facet	Vladimir V. Strelnikov Ekaterina B. Kuznetsova Alexander S. Tanas Viktoria V. Rudenko Alexey I. Kalinkin Elena V. Poddubskaya Tatiana V. Kekeeva Galina G. Chesnokova Ivan D. Trotsenko Sergey S. Larin Sergey I. Kutsev Dmitry V. Zaletaev Marina V. Nemtsova Olga A. Simonova
author_sort	Vladimir V. Strelnikov
title	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_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_sort	abnormal promoter dna hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9674b2bcc0154773b10c7499d5ce84fc
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Abnormal promoter DNA hypermethylation of the integrin, nidogen, and dystroglycan genes in breast cancer

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