The “Spot 14” gene resides on the telomeric end of the 11q13 amplicon and is expressed in lipogenic breast cancers: Implications for control of tumor metabolism

The “Spot 14” gene resides on the telomeric end of the 11q13 amplicon and is expressed in lipogenic breast cancers: Implications for control of tumor metabolism

Dartmouth Medical School, Departments of ^*Medicine, ^†Physiology, and ^‡Pathology, 1 Medical Center Drive, Lebanon, NH 03756

Communicated by William T. Wickner, Dartmouth Medical School, Hanover, NH (received for review January 27, 1998)

Abstract

Enhanced long chain fatty acid synthesis may occur in breast cancer, where it is necessary for tumor growth and predicts a poor prognosis. “Spot 14” (S14) is a carbohydrate- and thyroid hormone-inducible nuclear protein specific to liver, adipose, and lactating mammary tissues that functions to activate genes encoding the enzymes of fatty acid synthesis. Amplification of chromosome region 11q13, where the S14 gene (THRSP) resides, also predicts a poor prognosis in breast tumors. We localized the S14 gene between markers D11S906 and D11S937, at the telomeric end of the amplified region at 11q13, and found that it was amplified and expressed in breast cancer-derived cell lines. Moreover, concordant expression of S14 and a key lipogenic enzyme (acetyl-CoA carboxylase) in a panel of primary breast cancer specimens strongly supported a role for S14 as a determinant of tumor lipid metabolism. S14 expression provides a pathophysiological link between two prognostic indicators in breast cancer: enhanced lipogenesis and 11q13 amplification.

Footnotes

↵ § To whom reprint requests should be addressed. e-mail: William.B.Kinlaw.III{at}Hitchcock.org.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. 5446138 and 119329).
ABBREVIATIONS:

S14,

Spot 14;

CCND1,

cyclin D1;

IFNG,

interferon-γ;

FAS,

fatty acid synthase;

RT,

reverse transcription;

HSR,

homogeneously staining region;

YAC,

yeast artificial chromosome;

ACC,

acetyl-CoA carboxylase;

FCS,

fetal calf serum;

UCP3,

uncoupling protein 3;

TCRBC,

T-cell antigen receptor constant β-chain