L'isoforma Brd4-S(a) influenza l'aggressività e la migrazione cellulare nel tumore al seno

The Bromodomain-containing Protein 4 (Brd4) is an epigenetic reader and a transcriptional regulator. It is an important member of the Bromodomain and Extra-Terminal domain (BET) protein family and it is involved in the cell cycle progression. Its function is essential to overcome the G1 phase: this protein seems to have a role in regulating also the transcription of onco-genes and genes related with inflammation. Brd4 has been identified as a therapeutic target in acute myeloid leukaemia, multiple myeloma, Burkitt's lymphoma, NUT midline carcinoma, colon cancer, breast cancer and inflammatory diseases; although, its role in all these diseases is not clear. The reason could be that Brd4 has different isoforms with different functions. The most important isoforms are: Brd4 Long isoform (Brd4-L), two Brd4 short isoform (Brd4-S(a), Brd4-S(b)) and Brd4-NUT and each one possesses the same amino acid sequence used to recognize the histone acetylation but different activity. Recently, Brd4 has been reported as a possible target in triple negative breast cancer (TNBC), but some aspects remain cryptic, in particular the function of its short isoforms. Kellner and colleagues studied two proteins homologous to Brd4 in Drosophila, a short one and a long one, showing a different binding profile for each form and also slightly different functions. So we focused our attention on these two isoforms, Brd4-L and Brd4-S(a), in breast cancer. Our preliminary studies, conducted on three different cell lines (MCF-12F, MCF-7 and MDA-MB-231), demonstrate that the short isoform S(a), only expressed in tumor cancer cells, confers them a more aggressive behaviour. Thus, our results indicate that Brd4-S(a) could support Brd4-L action favour a misregulation in malignant cell line's genes expression.