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

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.

• Authors: Gaëlle Judes, Lucas Dubois, Khaldoun Rifaï, Mouhamed Idrissou, Florence Mishellany, Amaury Pajon, Sophie Besse, Marine Daures, Françoise Degoul, Yves-Jean Bignon, Frédérique Penault-Llorca, Dominique Bernard-Gallon
• Journal: Epigenomics (Epigenomics) Vol. 10 Issue 11 Pg. 1415-1430 (11 2018) ISSN: 1750-192X [Electronic] England
• PMID: 30324811 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Histones
• KAT5 protein, human
• Lysine Acetyltransferase 5

Topics

• Acetylation
• Animals
• Breast Neoplasms (genetics, metabolism)
• Female
• Histone Code
• Histones (metabolism)
• Humans
• Lysine Acetyltransferase 5 (genetics, metabolism)
• MCF-7 Cells
• Mice
• Mice, Inbred BALB C
• Mice, Nude