TIP60: an actor in acetylation of H3K4 and tumor development in breast cancer

• Published in: Epigenomics Vol. 10; no. 11; pp. 1415 - 1430
• Main Authors: Judes, Gaëlle, Dubois, Lucas, Rifaï, Khaldoun, Idrissou, Mouhamed, Mishellany, Florence, Pajon, Amaury, Besse, Sophie, Daures, Marine, Degoul, Françoise, Bignon, Yves-Jean, Penault-Llorca, Frédérique, Bernard-Gallon, Dominique
• Format: Journal Article
• Language: English
• Published: England Future Medicine Ltd 01.11.2018; Future Medicine
• Subjects: Acetylation; Acetyltransferase; acetyltransferase TIP60; Animals; Binding sites; Brain cancer; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer; Cell cycle; Chromatin; Deoxyribonucleic acid; DNA; DNA methylation; Female; Gene expression; Genomes; H3K4ac; Histone Code; Histones - metabolism; Humans; Immunoglobulins; Immunoprecipitation; Life Sciences; Lysine Acetyltransferase 5 - genetics; Lysine Acetyltransferase 5 - metabolism; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Molecular modelling; RNA polymerase; Studies; Target recognition; Tumor cell lines; Tumorigenesis; Tumors; Xenografts; Xenotransplantation; United States > US; H3K4ac; breast cancer; acetyltransferase TIP60
• ISSN: 1750-1911; 1750-192X
• DOI: 10.2217/epi-2018-0004

The acetyltransferase TIP60 is reported to be downregulated in several cancers, in particular breast cancer, but the molecular mechanisms resulting from its alteration are still unclear. In breast tumors, H3K4ac enrichment and its link with TIP60 were evaluated by chromatin immunoprecipitation-qPCR and re-chromatin immunoprecipitation techniques. To assess the biological roles of TIP60 in breast cancer, two cell lines of breast cancer, MDA-MB-231 (ER-) and MCF-7 (ER+) were transfected with shRNA specifically targeting TIP60 and injected to athymic Balb-c mice. We identified a potential target of TIP60, H3K4. We show that an underexpression of TIP60 could contribute to a reduction of H3K4 acetylation in breast cancer. An increase in tumor development was noted in sh-TIP60 MDA-MB-231 xenografts and a slowdown of tumor growth in sh-TIP60 MCF-7 xenografts. This is evidence that the underexpression of TIP60 observed in breast cancer can promote the tumorigenesis of ER-negative tumors.