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Spot 14: A Marker of Aggressive Breast Cancer and a Potential Therapeutic Target

Departments of Medicine (W.B.K., J.L.Q., C.R.-J., J.T.M.) and Pathology (W.A.W.) and the Norris Cotton Cancer Center (W.B.K., J.L.Q., W.A.W., C.R.-J.), Dartmouth Medical School, Lebanon, New Hampshire 03756; and Department of Pathology (J.T.M.), Walter Reed Army Medical Center, Silver Spring, Maryland 20910

Address all correspondence and requests for reprints to: William B. Kinlaw, M.D., Dartmouth Medical School, Norris Cotton Cancer Center, 606 Rubin Building, 1 Medical Center Drive, Lebanon, New Hampshire 03756. E-mail: william.kinlaw{at}hitchcock.org.

Spot 14 (S14) is a nuclear protein that communicates the status of dietary fuels and fuel-related hormones to genes required for long-chain fatty acid synthesis. In mammary gland, S14 is important for both epithelial proliferation and milk fat production. The S14 gene is amplified in some breast cancers and is strongly expressed in most. High expression of S14 in primary invasive breast cancer is conspicuously predictive of recurrence. S14 mediates the induction of lipogenesis by progestin in breast cancer cells and accelerates their growth. Conversely, S14 knockdown impairs de novo lipid synthesis and causes apoptosis. We found that breast cancer cells do not express lipoprotein lipase (LPL) and hypothesize that they do not have access to circulating lipids unless the local environment supplies it. This may explain why primary breast cancers with low S14 do not survive transit from the LPL-rich mammary fat pad to areas devoid of LPL, such as lymph nodes, and thus do not appear as distant metastases. Thus, S14 is a marker for aggressive breast cancer and a potential target as well. Future effort will center on validation of S14 as a therapeutic target and producing antagonists of its action.

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