INVESTIGADORES
PODESTA Ernesto Jorge
congresos y reuniones científicas
Título:
ROLE OF INTRAMITOCHONDRIAL ARACHIDONIC ACID IN BREAST CANCER CELLS
Autor/es:
DUARTE A1, ORLANDO U1, CASTILLO AF1, DELETTIERES D1, SOLANO AR1 PASQUALINI ME2, MALOBERTI P1, PODESTÁ EJ
Lugar:
Cordoba
Reunión:
Congreso; Sociedad Argentina de Investigaciones Bioquímicas y Biologia Molecular; 2008
Institución organizadora:
ACID IN BREAST CANCER CELLS
Resumen:
The inducible isoform of cycloxygenase COX-2 and the 5-, 12- and
15-lipoxygenases (LOX) are highly expressed in aggressive
metastatic breast cancer. The acyl-CoA sinthetase (ACS4), a key
enzyme in the regulation of intramitochondrial arachidonic acid
(AA) release, has been implicated in colon carcinoma and
hepatocellular cancer. The mechanism proposed for the role of
ACS4 is the reduction of free AA levels and apoptosis. Since ACS4
is working in AA release and its metabolism to the LOX pathway, an
important question is whether this mechanism is also operating in
breast cancer cells. We measured the levels of 5-, 12-,15-HETE by
HPLC in different human breast cancer cells line: MCF-7 (non
aggressive phenotype) and in the MDA-MB-231 (aggressive
phenotype). In MDA-MB-231 the levels of 5-,12-,15-HETE were
70, 5 and 2-fold higher than MCF7 cells. Inhibition of ACS4
expression in the aggressive cell line by siRNA reduced the LOX
products to the levels observed in the non aggressive cell line.
Overexpression of ACS4 in the non aggressive cell line produced an
increase in COX2 expression that was blocked by the inhibition of
LOX. The overexpression of ACS4 and COX2 correlates with the
high aggressive phenotype. These results indicate that ACS4 is a key
enzyme in the regulation of the synthesis of LOX products and
COX-2 induction, a key enzyme in cancer progression.