ANALYSIS OF TYPICAL AND ATYPICAL MAPK PHOSPHATASES (MKPS) EXPRESSION IN THE AGGRESSIVE PHENOTYPE OF BREAST CANCER CELLS.

MORI SEQUEIROS GARCÍA, MARÍA DE LAS MERCEDES; ORLANDO ULISES; CASTILLO ANA FERNANDA; COHEN SABBAN JUAN MANUEL; MALOBERTI PAULA; PAZ CRISTINA

Congreso; LXI REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INVESTIGACIÓN CLÍNICA (SAIC); 2016

MKPs are a heterogeneous group of dual-specificity phosphatases(DUSP) that can dephosphorylate both phosphotyrosineand phosphoserine/ phosphothreonine residues. This group ofenzymes includes typical MKPs (such as MKP-1, 2 and 3), whichspecifically dephosphorylate members of the MAPK family, andatypical MKPs (such as DUSP15, 18, 22), much less characterizedthan the first group. A large number of phosphatases are involvedin tumor development, pointing to a central role of this group ofenzymes in the regulation of proliferation and cell differentiation.The expression of acyl-CoA synthetase 4 (ACSL4), an enzyme thatparticipates in arachidonic acid metabolism, has been associated with more aggressive forms of several types of cancer. ACSL4 ispart of the mechanism responsible for increased breast cancer cellproliferation, invasion and migration. Thus, the aim of this workwas to analyze the expression of a typical, MKP-3, and an atypicalMKP, DUSP18, in cells with different ACSL4 expression levels. Theexperimental model is based on the stable transfection of MCF-7cells with ACSL4 using the tetracycline Tet-Off system (MCF-7Tet-Off/ACSL4), in which doxycycline down-regulates ACSL4 expression.mRNA levels of MKP-3 and DUSP18 were evaluated bysemiquantitative RT-PCR. The expression of MKP-3 and DUSP18was increased 1.5 and 1.8-fold (P