Abstract
The association between intratumoral cholesteryl ester (CE) and tumor progression has been reported previously. The objective of our study was to investigate a causal effect of CE on mammary tumor progression. Using MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice and breast tumor cell MCF-7, we show that both exogenous and endogenous CE can increase mammary tumor growth, that CE upregulates the AKT/mTOR pathway, and that CE synthesis blockade suppresses this signaling pathway. Our data suggest that SOAT1, a sterol O-acyltransferase, may be a potential target for the treatment of breast cancer.
Keywords:
SOAT1; avasimibe; breast cancer; cholesteryl ester.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cholesterol Esters / genetics
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Cholesterol Esters / metabolism*
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Female
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Humans
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MCF-7 Cells
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Mammary Neoplasms, Animal / drug therapy
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Mammary Neoplasms, Animal / genetics
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Mammary Neoplasms, Animal / metabolism*
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Mammary Neoplasms, Animal / pathology
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Mice
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Mice, Transgenic
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Proto-Oncogene Proteins c-akt / genetics
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Proto-Oncogene Proteins c-akt / metabolism*
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Signal Transduction*
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Sterol O-Acyltransferase / genetics
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Sterol O-Acyltransferase / metabolism*
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TOR Serine-Threonine Kinases / genetics
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TOR Serine-Threonine Kinases / metabolism*
Substances
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Cholesterol Esters
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Sterol O-Acyltransferase
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sterol O-acyltransferase 1
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mTOR protein, mouse
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Proto-Oncogene Proteins c-akt
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TOR Serine-Threonine Kinases