INVESTIGADORES
PODESTA Ernesto Jorge
congresos y reuniones científicas
Título:
A STABLE INDUCIBLE CELL LINE: ROLE OF ACYL-COA SYNTHETASE IN BREAST CANCER CELLS
Autor/es:
ORLANDO U1, DUARTE A1, KARLES C1, CORNEJO MACIEL F1, PAZ C1,PASQUALINI ME2, MALOBERTI P1, PODESTÁ EJ1.
Lugar:
Cordoba
Reunión:
Congreso; Sociedad Argentina de Investigaciones Bioquímica y Biologia Molecular; 2008
Institución organizadora:
Pasqualini ME2, Maloberti P1, Podestá EJ1.
Resumen:
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.