A novel murine xenograft model for the study of human breast cancer.

ORLANDO ULISES; GARONA J; RIPOLL G; ALONSO D; GOMEZ D; DUARTE ALEJANDRA; MALOBERTI PAULA; SOLANO ANGELA; PODESTÁ ERNESTO J.

San Luis

Congreso; XLVII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2011

A number of studies investigating the role of COX-2 in breast cancer are based on models exhibiting endogenously high COX-2 levels. The benefit of COX-2 inhibitors is being seen as a great promise in cancer therapy however, there have been recent concerns about potential cardiotoxicity. The aim of our study was to develop a novel murine xenograft model of human breast cancer based on a cell line, MCF-7, that fails to form tumors when injected into female athymic mice due to its low aggressive phenotype and on the MDA-MB-231 cell line, known to form tumors upon injection. Stable transfection of MCF-7 cells with the acyl-CoA synthetase 4 (ACSL4) cDNA transformed cells from a non-aggressive into a highly aggressive phenotype providing first-time evidence on the key role of ACSL4 in the regulation of COX-2 expression and on the proliferation and metastatic potential of cancer cells. Injection of ACSL4- transformed MCF-7 cells to female athymic mice resulted in the development of mammary tumors. Treatment of MDA-MB-231 tumor-bearing mice with a  combination of ACSL4, LOX and COX- 2 inhibitors resulted in a significant reduction of tumor growth with a sinergystic effect of the inhibitors. We conclude that this murine xenograft model of breast cancer may be useful for the evaluation of preclinical safety and efficacy of novel adjuvant therapies for women with metastastic breast cancer.