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.
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Acknowledgements
The authors thank our imaging facility, Imagerie Confocale de Clermont-Ferrand (ICCF) and we gratefully acknowledge the help of C Vachias. We thank M Roche and J Allemand for the immunohistochemical technique.
Financial & competing interests disclosure
We thank the ‘Ligue contre le cancer-Comité du Puy-de-Dôme’. K. Rifaï was funded by the Hariri Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Ethical conduct of research
For in vivo xenograft models, all protocols were conducted in accordance with the 2010/63/UE Directive after approval by the institutional review board C2E2A from Auvergne Region (approval number: APAFIS#3399-201601 1 109302187 vS). The samples were obtained from a Biological Resources Center (BB-0033-00075) and a prior signed informed consent was obtained from each patient. It was done in accordance with the Council of Europe’s Recommendation on Research on Biological Materials of Human Origin (Rec [2006]) from 2006.