Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors
| Autor: | Sergei V. Sidorov, Dina Loginova, Pavel V. Vavilov, Valentina I. Rykova, Vladimir I. Kashuba, Tatiana Y. Prudnikova, Tatiana V. Pavlova, Luydmila A. Mostovich, Aleksandr G. Kondratov, Elvira V. Grigorieva, Eugene R. Zabarovsky |
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| Rok vydání: | 2011 |
| Předmět: |
ITGA9
Angiogenesis Integrin Down-Regulation Breast Neoplasms Decitabine Hydroxamic Acids Epigenesis Genetic Cellular and Molecular Neuroscience Tumor Cells Cultured otorhinolaryngologic diseases Humans Gene Silencing skin and connective tissue diseases biology Cell migration Cell Biology DNA Methylation Epigenetic silencing Lymphangiogenesis Cell biology Azacitidine biology.protein CpG Islands Female Integrin beta 6 sense organs Integrin alpha Chains human activities Human breast Research Paper |
| Zdroj: | Cell Adhesion & Migration. 5:395-401 |
| ISSN: | 1933-6926 1933-6918 |
| DOI: | 10.4161/cam.5.5.17949 |
| Popis: | Integrin alpha9 (ITGA9) is one of the less studied integrin subunits that facilitates accelerated cell migration and regulates diverse biological functions such as angiogenesis, lymphangiogenesis, cancer cell proliferation and migration. In this work, integrin alpha9 expression and its epigenetic regulation in normal human breast tissue, primary breast tumors and breast cancer cell line MCF7 were studied. It was shown that integrin alpha9 is expressed in normal human breast tissue. In breast cancer, ITGA9 expression was downregulated or lost in 44% of tumors while another 45% of tumors showed normal or increased ITGA9 expression level (possible aberrations in the ITGA9 mRNA structure were supposed in 11% of tumors). Methylation of ITGA9 CpG-island located in the first intron of the gene was shown in 90% of the breast tumors with the decreased ITGA9 expression while no methylation at 5′-untranslated region of ITGA9 was observed. 5-aza-dC treatment restored integrin alpha9 expression in ITGA9-negative MCF7 breast carcinoma cells, Trichostatin A treatment did not influenced it but a combined treatment of the cells with 5-aza-dC/Trichostatin A doubled the ITGA9 activation. The obtained results suggest CpG methylation as a major mechanism of integrin alpha9 inactivation in breast cancer with a possible involvement of other yet unidentified molecular pathways. |
| Databáze: | OpenAIRE |
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