title: Integrin alpha9 (ITGA9) expression and epigenetic silencing in human breast tumors.
abstract: 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.
authors: Institute of Molecular Biology and Biophysics SD RAMS, Novosibirsk, Russia.
authors: Luydmila A
authors: LA
authors: Mostovich
authors: Tatiana Y
authors: TY
authors: Prudnikova
authors: Aleksandr G
authors: AG
authors: Kondratov
authors: Dina
authors: D
authors: Loginova
authors: Pavel V
authors: PV
authors: Vavilov
authors: Valentina I
authors: VI
authors: Rykova
authors: Sergei V
authors: SV
authors: Sidorov
authors: Tatiana V
authors: TV
authors: Pavlova
authors: Vladimir I
authors: VI
authors: Kashuba
authors: Eugene R
authors: ER
authors: Zabarovsky
authors: Elvira V
authors: EV
authors: Grigorieva
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D000077209:Decitabine; D015536:Down-Regulation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D005260:Female; D020868:Gene Silencing / Q000502:physiology*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D039001:Integrin alpha Chains / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D006877:Hydroxamic Acids; D039001:Integrin alpha Chains; C084613:integrin alpha9; C012589:trichostatin A; D000077209:Decitabine; D001374:Azacitidine