INVESTIGADORES
ALONSO Daniel Fernando
congresos y reuniones científicas
Título:
A murine xenograft model for the study of ciclooxygenase-2 expression and function in human breast cancer
Autor/es:
SOLANO AR; ORLANDO U; GARONA J; RIPOLL GV; DUARTE A; MALOBERTI P; AVAGNINA A; ALONSO DF; GOMEZ DE; PODESTA E
Reunión:
Simposio; Thirty-Fourth Annual CTRC-AACR San Antonio Breast Cancer Symposium; 2011
Resumen:
Ciclooxygenase-2 (COX-2) has been suggested as a necessary component of the cellular and molecular mechanisms behind breast cancer cell motility and invasion The potential therapeutic benefit of COX-2 inhibitors in a range of cancers is being seen as a great promise however, there have been recent concerns about potential cardiotoxicity. Thus, there is an urgency to develop new inhibitors exhibiting a better risk/benefit ratio. Acyl-CoA synthetase 4 (ACSL4), belongs to a five-member familyof enzymes that esterifies mainly arachidonic acid into acyl-CoA. We have provided first-time evidence demonstrating that, ACSL4 is the key enzyme that regulates the induction of COX-2, the production of prostaglandin E2 (PGE2) and the proliferation and metastatic potential of breast cancer cells. Therefore, the aim of the study was the development of an in vivo model of human breast tumor xenografts for the study of the regulation of COX-2 expression and action. Stable transfection of MCF-7 cells with ACSL4 cDNA under the control of tetracycline (MCF-7 Tet-off-ACSL4) resulted in a significant increase in the expression of COX-2. The increment in COX-2 expression registered in MCF-7 Tet-off-ACSL4 cells is accompanied with an increase in the production of PGE2, and the proliferation and metastatic potential of cancer cells. Next, we tested whether the injection of MCF-7 Tet-off/ACSL4 cells into nude mice resulted in tumor development. The results of those experiments demonstrate that MCF-7 Tet-off/ACSL4 cells develop into murine mammary tumors whereas cells transfected with the MCF-7 Tet-off empty vector did not. Interestingly, treatment of nude mice with tetracycline resulted in tumor growth inhibition. The results show that the sole transfection of ACSL4 results in a phenotype change that endows the cells with the capacity to develop into tumors when injected into nude mice. Tumor volume (TV) at day 70 reached 468.4 ± 189.3mm3. Treatment with tetracycline reduced TV to 189.3 ± 65.9mm3 (p