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

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 can...

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Published inEndocrinology (Philadelphia) Vol. 147; no. 9; pp. 4048 - 4055
Main Authors Kinlaw, William B, Quinn, Jennifer L, Wells, Wendy A, Roser-Jones, Christopher, Moncur, Joel T
Format Journal Article
LanguageEnglish
Published United States Endocrine Society 01.09.2006
Oxford University Press
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Abstract 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.
AbstractList 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.
Author Quinn, Jennifer L
Kinlaw, William B
Moncur, Joel T
Wells, Wendy A
Roser-Jones, Christopher
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Snippet 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...
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SubjectTerms Animal fat
Animals
Antagonists
Apoptosis
Biomarkers, Tumor
Breast cancer
Breast milk
Breast Neoplasms - chemistry
Breast Neoplasms - genetics
Breast Neoplasms - therapy
Cell proliferation
DNA, Complementary - genetics
Female
Hormones
Humans
Lipids
Lipids - biosynthesis
Lipogenesis
Lipoprotein lipase
Lymph nodes
Mammary gland
Mammary glands
Metastases
Mice
Nuclear fuels
Nuclear Proteins - analysis
Nuclear Proteins - genetics
Nuclear Proteins - physiology
Oligonucleotide Array Sequence Analysis
Progestin
Protein biosynthesis
Synthesis
Target spot
Therapeutic targets
Transcription Factors - analysis
Transcription Factors - genetics
Transcription Factors - physiology
Title Spot 14: A Marker of Aggressive Breast Cancer and a Potential Therapeutic Target
URI http://dx.doi.org/10.1210/en.2006-0463
https://www.ncbi.nlm.nih.gov/pubmed/16809441
https://www.proquest.com/docview/3130590976
https://search.proquest.com/docview/68753317
Volume 147
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