Gene Expression Profile and Signaling Pathways in MCF-7 Breast Cancer Cells Mediated by Acyl-Coa Synthetase 4 Overexpression

ANA F. CASTILLO; ULISES D. ORLANDO ; PAULA LOPEZ; ANGELA R. SOLANO; PAULA M. MALOBERTI ; ERNESTO J. PODESTA

Transcriptomics

OMICS International

Lugar: Los Angeles; Año: 2015 vol. 3 p. 1 - 26

2329-8936

Aim: Breast cancer comprises a heterogeneous group of diseases that vary in morphology, biology, behavior andresponse to therapy. Previous studies have identified an acyl-CoA synthetase 4 (ACSL4) gene-expression patterncorrelated with very aggressive tumors. In particular, we have used the tetracycline Tet-Off system to stably transfectnon-aggressive breast cancer MCF-7 cells and developed a stable line overexpressing ACSL4 (MCF-7 Tet-Off/ACSL4).As a result, we have proven that cell transfection solely with ACSL4 cDNA renders a highly aggressive phenotype invitro and results in the development of growing tumors when injected into nude mice. Nevertheless, and in spiteof widespread consensus on the role of ACSL4 in mediating an aggressive phenotype in breast cancer, the earlysteps through which ACSL4 increases tumor growth and progression have been scarcely described and need furtherelucidation. For this reason, the goal of this work was to study the gene expression profile and the signaling pathwaystriggered by ACSL4 overexpression in the mechanism that leads to an aggressive phenotype in breast cancer.Methods: We have performed a massive in-depth mRNA sequencing approach and a reverse-phase protein arrayusing MCF-7 Tet-Off/ACSL4 cells as a model to identify gene expression and functional proteomic signatures specificto ACSL4 overexpression.Results and Conclusion: The sole expression of ACSL4 displays a distinctive transcriptome and functionalproteomic profile. Furthermore, gene networks most significantly upregulated in breast cancer cells overexpressingACSL4 are associated to the regulation of embryonic and tissue development, cellular movement and DNA replicationand repair. In conclusion, ACSL4 is an upstream regulator of tumorigenic pathways. Because an aggressive tumorphenotype appears in the early stages of metastatic progression, the previously unknown mediators of ACSL4 mightbecome valuable prognostic tools or therapeutic targets in breast cancer.