Breast cancer is often sporadic due to several factors. Among them, the deregulation of epigenetic
proteins may be involved. TIP60 or KAT5 is an
acetyltransferase that regulates gene transcription through the
chromatin structure. This pleiotropic
protein acts in several cellular pathways by acetylating
proteins.
RNA and
protein expressions of TIP60 were shown to decrease in some
breast cancer subtypes, particularly in
triple-negative breast cancer (TNBC), where a low expression of TIP60 was exhibited compared with
luminal subtypes. In this study, the inhibition of the residual activity of TIP60 in
breast cancer cell lines was investigated by using two chemical inhibitors, TH1834 and
NU9056, first on the acetylation of the specific target,
lysine 4 of
histone 3 (H3K4) by immunoblotting, and second, by
chromatin immunoprecipitation (ChIP)-qPCR (-quantitative Polymerase Chain Reaction). Subsequently, significant decreases or a trend toward decrease of H3K4ac in the different
chromatin compartments were observed. In addition, the expression of 48 human
nuclear receptors was studied with TaqMan Low-Density Array in these
breast cancer cell lines treated with TIP60 inhibitors. The statistical analysis allowed us to comprehensively characterize the
androgen receptor and NR3C2 receptors in TNBC cell lines after TH1834 or
NU9056 treatment. The understanding of the residual activity of TIP60 in the evolution of
breast cancer might be a major asset in the fight against this disease, and could allow TIP60 to be used as a
biomarker or therapeutic target for
breast cancer progression in the future.