RAC3 levels are correlated with metalloproteinases and leptin expression in adipose tissue adjacent to breast tumours

LIRA, MARÍA CECILIA; MARINO, GABRIELA; RUBIO MARIA FERNANDA; ROSA, FRANCISCO DAMIÁN; SALAZAR GÜEMES, MARÍA CECILIA; SOAREZ MACHADO, MILENI; COSTAS MÓNICA A

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica; 2018

Sociedad Argentina de Investigación Clínica

RAC3 is a transcriptional coactivator that is present in low levels intonormal cells, almost undetectable, but it has been found amplified oroverexpressed in several types of cancer, including breast tumours.Previously, we demonstrated that RAC3 decreases during adipogenesis,favouring the process through an increase of autophagyand a decrease in the proliferative rate. In addition to the role ofthe coactivator during adipocyte differentiation, we have started tostudy the modulation of RAC3 in adipose tissue (AT) in breast cancercontext. We collected breast tumour-surrounding AT from IDIM?spatients (n=30) and, we have already demonstrated that the higherexpression of RAC3 in these samples, not only tumours had molecularcharacteristics with worse prognosis, but also were in a moreadvanced clinical stage. Given these results, the aim of this workwas to evaluate the correlation between RAC3 expression levelsand the expression of adipokines in AT.We assayed metalloproteinases (MMPs 2 and 9) activity by zymography,from conditioned mediums of AT adjacent to tumours,and determined there is greater activity in AT with higher levels ofRAC3. Even more, there is a correlation between MMP2 and RAC3levels measured by qPCR (y=0.76x + 0.94; R2=0.90). It is knownthat Leptin induces the expression of MMP2 and 9. Therefore, weconfirmed by qPCR that in our samples there is also a correlationbetween Leptin and MMP2 levels (y=9.12x - 7.93; R2=0.84). Furthermore,we compared RAC3 and Leptin expression in the samplesand we found that in those with RAC3 ratios above 5, there is higherLeptin expression (147.0+/-60.0) respect to AT with RAC3 ratios between5 and 1 (2.3+/-1.1), and below 1 (0.1+/-0.0) (p