REGULATION OF LIPID METABOLISM AND ONCOGENESIS

DUARTE ALEJANDRA; MALOBERTI PAULA; KARLES CRISTINA; ORLANDO ULISES; NEUMAN ISABEL; CORNEJO MACIEL FABIANA; SOLANO ANGELA R; PODESTÁ ERNESTO J

Mar del Plata, Buenos Aires, Argentina

Congreso; 43º Reunión Anual de la Sociedad Argentina de Investigaciones Bioquímicas y Biología Molecular; 2007

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB).

The translocator protein (TSPO), a mitochondrial acyl-CoA thioesterase (Acot2) and an arachidonic acid (AA) preferring acyl-CoA synthetase (ACS4) are important for cholesterol transport and regulation of intramitochondrialAAlevels in steroidogenic tissues. Some studies demonstrate the role of TSPO on the development of different types of cancer. The overexpression of TSPO correlates with the development of the aggressive phenotype of breast cancers, affecting cholesterol transport and cellular proliferation. It is known thatACS4 is overexpressed in hepatocarcinoma and colon cancer. In this work we studied the role of this enzyme, taking as model MCF7, a non aggressive and MDA-MB-231 a high aggressive breast cancer cell lines. The ACS4 levels expression correlate with the high cellular aggressiveness phenotype, as was previously described for TSPO levels in this cell lines. The overexpression ofACS4 produces a more aggressive cell phenotype, measured by proliferation, migration and cellular invasion. Moreover, we demonstrated that the intramitochondrialAAlevels are elevated in high aggressive cell lines. The overexpression ofACS4 in several types of tumors would support ACS4 as a potentially early tumor marker. This is in agreement with recently results where ACS4 is one protein that is increased during the transition from normal to preneoplastic mammary tissue.