Overexpression of fatty acid synthase in SKBR3 breast cancer cell line is mediated via a transcriptional mechanism

Overexpression of fatty acid synthase (FAS) in certain breast, prostate and ovarian tumors has been correlated with aggressive cancer phenotype and poor prognosis. The objective of this study was to use a breast cancer-derived cell line, SKBR3, as a model to define the underlying mechanism for overexpression of FAS in cancer cells. Different stages of gene expression where overproduction of FAS could potentially be achieved were investigated. Whereas gross chromosomal rearrangement at the FAS locus, amplification of the FAS gene, increases in FAS message stability and longer half-life of the FAS protein were not detected, an increase in the rate of transcription of the FAS gene, and consequently a higher abundance of FAS-mRNA, was found to be primarily responsible for FAS overexpression in this cell line.