THE SPOT-14 GENE RESIDES ON THE TELOMERIC END OF THE 11Q13 AMPLICON AND IS EXPRESSED IN LIPOGENIC BREAST CANCERS - IMPLICATIONS FOR CONTROLOF TUMOR METABOLISM

Enhanced long chain fatty acid synthesis may occur in breast cancer, w here it is necessary for tumor growth and predicts a poor prognosis. ' 'Spot 14'' (S14) is a carbohydrate- and thyroid hormone-inducible nucl ear protein specific to liver, adipose, and lactating mammary tissues that functions to activate genes encoding the enzymes of fatty acid sy nthesis. Amplification of chromosome region 11q13, where the S14 gene (THRSP) resides, also predicts a poor prognosis in breast tumors. We l ocalized the S14 gene between markers D11S906 and D11S937, at the telo meric end of the amplified region at 11q13, and found that it was ampl ified and expressed in breast cancer-derived cell lines, Moreover, con cordant expression of S14 and a key lipogenic enzyme (acetyl-CoA carbo xylase) in a panel of primary breast cancer specimens strongly support ed a role for S14 as a determinant of tumor lipid metabolism, S14 expr ession provides a pathophysiological link between two prognostic indic ators in breast cancer: enhanced lipogenesis and 11q13 amplification.