A STABLE INDUCIBLE CELL LINE: ROLE OF ACYL-COA SYNTHETASE IN BREAST CANCER CELLS

ORLANDO ULISES; DUARTE ALEJANDRA; KARLES CRISTINA; CORNEJO MACIEL FABIANA; PAZ CRISTINA; PASQUALINI MARIA EUGENIA; MALOBERTI PAULA; PODESTÁ ERNESTO J

Villa Carlos Paz, Córdoba, Argentina

Congreso; XLIV Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2008

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

Previously we demonstrated that the levels of an acyl-CoA synthetase (ACS4) correlate with aggressive cellular phenotype measured by cellular proliferation, migration and invasion. Taking MCF-7 and MDA-MB-231 cell lines as models of non-aggressive and aggressive human breast cancer, we showed that the aggressiveness of the cells changes by knocking down the expression of ACS4 by transient transfection of siRNA in MDAMB-231 cells or by ACS4 overexpression in MCF-7 cells. Here we confirm these results generating a stable inducible cell line of MCF7, where overexpression of ACS4 can be switched off by tetracycline. MCF-7 cells were transfected with a regulator plasmid (pTet-Off) containing the tetracycline controlled transactivator and neomycin resistance. The selected clones were transfected with a responsive plasmid (pTRE) containing ACS4 cDNA and puromicin resistance. In the resulting stable cell line, ACS4 levels were 14-fold higher than MCF-7 non transfected or tetracycline treated cells. ACS4 levels correlated with the aggressiveness of the stable cell line measured by cellular proliferation and migration. ACS4 is part of the mechanism of COX-2 induction, an enzyme that plays a critical role in cancer progression. The combined use of inhibitors of both enzymes could be a potential approach of breast cancer treatment reducing the non desirable effect of COX-2 inhibitors.