1. TIP60: an actor in acetylation of H3K4 and tumor development in breast cancer
- Author
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Dominique Bernard-Gallon, Françoise Degoul, Yves-Jean Bignon, Florence Mishellany, Marine Daures, Lucas Dubois, Sophie Besse, Amaury Pajon, Khaldoun Rifaï, Frédérique Penault-Llorca, Gaëlle Judes, Mouhamed Idrissou, Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Département d'Oncogénétique, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER-UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER, and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
0301 basic medicine ,Cancer Research ,Immunoprecipitation ,education ,Mice, Nude ,Breast Neoplasms ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,macromolecular substances ,Biology ,medicine.disease_cause ,Lysine Acetyltransferase 5 ,Histones ,acetyltransferase TIP60 ,Small hairpin RNA ,Mice ,03 medical and health sciences ,breast cancer ,Breast cancer ,Genetics ,medicine ,Animals ,Humans ,skin and connective tissue diseases ,Mice, Inbred BALB C ,Acetylation ,Transfection ,medicine.disease ,3. Good health ,Chromatin ,Histone Code ,030104 developmental biology ,Acetyltransferase ,MCF-7 Cells ,Cancer research ,Female ,H3K4ac ,Carcinogenesis - Abstract
Aim: 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. Materials & methods: 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. Results: 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. Conclusion: This is evidence that the underexpression of TIP60 observed in breast cancer can promote the tumorigenesis of ER-negative tumors.
- Published
- 2018
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