Abstract
Background:
Osteosarcoma is the most common primary bone malignancy of adolescents and young adults.
Methods:
We analyzed liver X receptor α (LXRα) mRNA expression in 16 pairs of human osteosarcoma tissues and adjacent noncancerous tissues. Moreover, we investigated LXRα's potential role in regulating cell proliferation in Saos-2 and U2OS cells.
Results:
We found that activation of LXRα, a member of nuclear receptor, was able to inhibit cell proliferation in Saos-2 and U2OS cells. At the molecular level, our results further revealed that expression of tumor suppressor gene, FoxO1, was up-regulated by LXRα activation. LXRα activates FoxO1 transcription through a direct binding on its promoter region.
Conclusion:
LXRα acts as a tumor suppressor for osteosarcoma, which may offer a new way in molecular targeting cancer treatment.
Copyright © 2013 S. Karger AG, Basel.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Binding Sites
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Cell Line, Tumor
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Cell Proliferation
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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Cyclin-Dependent Kinase Inhibitor p27 / genetics
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Cyclin-Dependent Kinase Inhibitor p27 / metabolism
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Forkhead Box Protein O1
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism*
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Humans
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Liver X Receptors
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Orphan Nuclear Receptors / genetics
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Orphan Nuclear Receptors / metabolism*
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Osteosarcoma / metabolism
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Osteosarcoma / pathology
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Promoter Regions, Genetic
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RNA Interference
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RNA, Messenger / metabolism
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RNA, Small Interfering / metabolism
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Transcription, Genetic
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Up-Regulation
Substances
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Cyclin-Dependent Kinase Inhibitor p21
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FOXO1 protein, human
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Forkhead Box Protein O1
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Forkhead Transcription Factors
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Liver X Receptors
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NR1H3 protein, human
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Orphan Nuclear Receptors
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RNA, Messenger
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RNA, Small Interfering
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Cyclin-Dependent Kinase Inhibitor p27