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Epigenomics. 2018 Nov;10(11):1415-1430. doi: 10.2217/epi-2018-0004. Epub 2018 Oct 16.

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

Author information

1
Department of Oncogenetics, Centre Jean Perrin, CBRV, 28 Place Henri-Dunant, 63001, Clermont-Ferrand, France.
2
INSERM U 1240, IMOST, University Clermont Auvergne, 58 rue Montalembert-BP184, 63005 Clermont-Ferrand, France.
3
Department of Biopathology, Centre Jean Perrin, 58 rue Montalembert, 63011, Clermont-Ferrand, France.

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.

KEYWORDS:

H3K4ac; acetyltransferase TIP60; breast cancer

PMID:
30324811
DOI:
10.2217/epi-2018-0004
[Indexed for MEDLINE]

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