Preview

Medical Genetics

Advanced search

DNA methylation of the integrin, nidogen and dystroglycan genes in normal and breast carcinoma tissues

https://doi.org/10.1234/XXXX-XXXX-2016-1-13-20

Abstract

Transmembrane cellular receptors and extracellular matrix components play a fundamental role in regulation of cellular activity, and providing concerted integration of the cells in the tissue structure. We have analyzed DNA methylation at the promoter regions of eight integrin genes ( ITGA1, ITGA2, ITGA3, ITGA4, ITGA6, ITGA7, ITGA9, ITGB1 ), two nidogen genes and a dystroglycan gene in normal breast tissue, as well as in the breast carcinoma samples. Integrin and dystroglycan are transmembrane receptors; nidogens are components of the extracellular matrix. The protein products of these genes are able to interact with proteins of the basement membrane LAMA1, LAMA2 and LAMB1; abnormal methylation of the LAMA1 , LAMA2 and LAMB1 genes in breast cancer had been described in our previous publications. Abnormal methylation frequencies at the promoter regions of genes ITGA1 , ITGA4 , ITGA7 , ITGA9 , NID1 and NID2 in breast cancer accounted for 13.3%, 29.3%, 3.3%, 40.6%, 37.3%, 39.3%, respectively. In our study cohort, DNA methylation at promoter regions of the ITGA4 , ITGA9 and NID1 genes was enriched in HER2 positive tumors, a highly aggressive form of breast cancer.

About the Authors

O. A. Simonova
«Медико-генетический научный центр»
Russian Federation


E. B. Kuznetsova
«Медико-генетический научный центр»; Первый Московский государственный медицинский университет им. И.М. Сеченова
Russian Federation


A. S. Tanas
«Медико-генетический научный центр»; Российский национальный исследовательский медицинский университет им. Н.И. Пирогова
Russian Federation


V. V. Rudenko
«Медико-генетический научный центр»
Russian Federation


E. V. Poddubskaya
«Российский онкологический научный центр им. Н.Н. Блохина»
Russian Federation


T. V. Kekeeva
«Медико-генетический научный центр»
Russian Federation


R. A. Kerimov
«Российский онкологический научный центр им. Н.Н. Блохина»
Russian Federation


I. D. Trotsenko
Российский университет дружбы народов Министерства образования и науки Российской Федерации
Russian Federation


E. A. Alekseeva
«Медико-генетический научный центр»
Russian Federation


D. V. Zaletaev
«Медико-генетический научный центр»; Первый Московский государственный медицинский университет им. И.М. Сеченова; Российский национальный исследовательский медицинский университет им. Н.И. Пирогова
Russian Federation


V. V. Strelnikov
«Медико-генетический научный центр»; Российский национальный исследовательский медицинский университет им. Н.И. Пирогова
Russian Federation


References

1. Риппа А.Л., Воротеляк Е.А., Васильев А.В. и др. Роль интегринов в формировании и гомеостазе эпидермиса и придатков кожи // Acta Naturae. - 2013. - Т. 5, № 4(19). - С. 24-36.

2. Симонова О.А., Кузнецова Е.Б., Поддубская Е.В. и др. Гены ламининов, конститутивно и аномально метилированные при раке молочной железы // Молекулярная биология. - 2015. - Т. 49, № 4. - С. 667-677.

3. Bader B.L., Smyth N., Nedbal S. et al. Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice // Mol. Cell Biol. - 2005. - Vol. 25(15). - P. 6846-6856.

4. Brown M.C., Staniszewska I., Lazarovici P. et al. Regulatory effect of nerve growth factor in alpha9beta1 integrin-dependent progression of glioblastoma // Neuro Oncol. - 2008. - Vol. 10(6). - P. 968-980.

5. Chang E., Park D.I., Kim Y.J. et al. Detection of colorectal neoplasm using promoter methylation of ITGA4, SFRP2, and p16 in stool samples: a preliminary report in Korean patients // Hepatogastroenterology. - 2010. - Vol. 57(101). - P. 720-727.

6. Deb M., Sengupta D., Patra S.K. Integrin-epigenetics: a system with imperative impact on cancer // Cancer Metastasis Rev. - 2012. - Vol. 31. - P. 221-234.

7. Do S.I., Ko E., Kang S.Y. et al. Aberrant DNA methylation of integrin a4 in human breast cancer // Tumour Biol. - 2014. - Vol. 35(7). - P. 7079-7084.

8. Egeblad M., Nakasone E.S., Werb Z. Tumors as organs: complex tissues that interface with the entire organism // Dev Cell. - 2010. - Vol. 18(6). - P. 884-901.

9. Fiorilli P., Partridge D., Staniszewska I. et al. Integrins mediate adhesion of medulloblastoma cells to tenascin and activate pathways associated with survival and proliferation // Lab. Invest. - 2008. - Vol. 88. - P. 1143-1156.

10. Glukhova M.A., Streuli C.H. How integrins control breast biology // Curr. Opin. Cell Biol. - 2013. - Vol. 25(5). - P. 633-641.

11. Gosslar U., Jonas P., Luz A. et al. Predominant role of alpha 4-integrins for distinct steps of lymphoma metastasis // Proc. Natl. Acad. Sci. U.S.A. - 1996. - Vol. 93(10). - P. 4821-4826.

12. Hitchins M.P., Lin V.A., Buckle A. et al. Epigenetic inactivation of a cluster of genes flanking MLH1 in microsatellite-unstable colorectal cancer // Cancer Res. - 2007. - Vol. 67. - P. 9107-9116.

13. Ho M.S., Bоse K., Mokkapati S. et al. Nidogens-Extracellular matrix linker molecules // Microsc. Res. Tech. - 2008. - Vol. 71(5). - P. 387-395.

14. Kianpour S., Mokaram P., Dehghani M. et al. Aberrant methylation of integrin a4 and e-cadherin using laser capture microdissection of prostate tissue // Cell Journal (Yakhteh) - 2011. - Vol. 13 (Supp. 2). - P. 43-44.

15. Klemke M., Weschenfelder T., Konstandin M.H. et al. High affinity interaction of integrin alpha4beta1 (VLA-4) and vascular cell adhesion molecule 1 (VCAM-1) enhances migration of human melanoma cells across activated endothelial cell layers // J. Cell Physiol. - 2007. - Vol. 212(2). - P. 368-374.

16. Kohfeldt E., Sasaki T., Gоhring W. et al. Nidogen-2: a new basement membrane protein with diverse binding properties // J. Mol. Biol. - 1998. - Vol. 282(1). - P. 99-109.

17. Lee E.J., Lee B.B., Han J. et al. CpG island hypermethylation of E-cadherin (CDH1) and integrin alpha4 is associated with recurrence of early stage esophageal squamous cell carcinoma // Int. J. Cancer. - 2008. - Vol. 123. - P. 2073-2079.

18. Meyer C., Brieger A., Plotz G. et al. An interstitial deletion at 3p21.3 results in the genetic fusion of MLH1 and ITGA9 in a Lynch syndrome family // Clin. Cancer Res. - 2009. - Vol. 15. - P. 762-769.

19. Mitra S., Mazumder Indra D., Bhattacharya N. et al. RBSP3 is frequently altered in premalignant cervical lesions: clinical and prognostic significance // Genes Chromosomes Cancer. - 2010. - Vol. 49(2). - P. 155-170.

20. Mokkapati S., Bechtel M., Reibetanz M. et al. Absence of the Basement Membrane Component Nidogen 2, but Not of Nidogen 1, Results in Increased Lung Metastasis in Mice // J. Histochem. Cytochem. - 2012. - Vol. 60(4). - P. 280-289.

21. Mostovich L.A., Prudnikova T.Y., Kondratov A.G. et al. Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors // Cell Adh. Migr. - 2011. - Vol. 5(5). - P. 395-401.

22. Muschler J., Levy D., Boudreau R. et al. A role for dystroglycan in epithelial polarization: loss of function in breast tumor cells // Cancer Res. - 2002. - Vol. 62(23). - P. 7102-7109.

23. Park J., Song S.H., Kim T.Y. et al. Aberrant methylation of integrin alpha4 gene in human gastric cancer cells // Oncogene. - 2004. - Vol. 23. - P. 3474-3480.

24. Pujuguet P., Simian M., Liaw J. et al. Nidogen-1 regulates laminin-1-dependent mammary-specific gene expression // J. Cell Sci. - 2000. - Vol. 113. - P. 849-858.

25. Qian F., Vaux D.L., Weissman I.L. Expression of the integrin a4b1 on melanoma cells can inhibit the invasive stage of metastasis formation // Cell. - 1994. - Vol. 77(3). - P. 335-347.

26. Taichman D.B., Cybulsky M.I., Djaffar I. et al. Tumor cell surface alpha 4 beta 1 integrin mediates adhesion to vascular endothelium: demonstration of an interaction with the N-terminal domains of INCAM-110/VCAM-1 // Cell Regul. - 1991. - Vol. 2(5). - P. 347-355.

27. Uhm K.O., Lee J.O., Lee Y.M. et al. Aberrant DNA methylation of integrin alpha4: a potential novel role for metastasis of cholangiocarcinoma // J. Cancer Res. Clin. Oncol. - 2010. - Vol. 136(2). - P. 187-194.

28. Ulazzi L., Sabbioni S., Miotto E. et al. Nidogen 1 and 2 gene promoters are aberrantly methylated in human gastrointestinal cancer // Mol. Cancer. - 2007. - Vol. 28. - P. 6-17.

29. Wehrle-Haller B., Imhof B.A. Integrin-dependent pathologies // J. Pathol. - 2003. - Vol. 200(4). - P. 481-487.

30. Weir M.L., Oppizzi M.L., Henry M.D. et al. Dystroglycan loss disrupts polarity and beta-casein induction in mammary epithelial cells by perturbing laminin anchoring // J. Cell Sci. - 2006. - Vol. 119. - P. 4047-4058.


Review

For citations:


Simonova O.A., Kuznetsova E.B., Tanas A.S., Rudenko V.V., Poddubskaya E.V., Kekeeva T.V., Kerimov R.A., Trotsenko I.D., Alekseeva E.A., Zaletaev D.V., Strelnikov V.V. DNA methylation of the integrin, nidogen and dystroglycan genes in normal and breast carcinoma tissues. Medical Genetics. 2016;15(1):13-20. (In Russ.) https://doi.org/10.1234/XXXX-XXXX-2016-1-13-20

Views: 597


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2073-7998 (Print)