Abstract
The molecular mechanism underlying thyroid hormone inhibition of thyrotrope cell growth is poorly understood. A comprehensive screen for T3-regulated genes involved in thyrotrope cell regulation was performed by Affymetrix MGU74A Genechip microarray analyses, which compared total RNA from hypothyroid versus 24 h T3-treated TtT-97 tumors. Of the 13,000 genes screened, a number of novel, T3-responsive candidate genes were identified. Within the Wnt family of growth factors, only Wnt-10A transcripts were abundantly expressed in hypothyroid TtT-97 tumors, and were down-regulated with T3 by 6 h of treatment. In addition, nuclear beta-catenin, which is a downstream mediator of canonical Wnt signaling, was decreased at the protein and functional levels. TtT-97 growth suppression was associated with decreased cyclin A transcript levels. We conclude that treatment of thyrotropic TtT-97 tumors with T3 resulted in the decreased expression of Wnt-10A, and that thyroid hormone may inhibit growth via cyclin A regulation.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Line, Tumor / drug effects
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Down-Regulation
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic / drug effects*
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Genes, cdc / drug effects
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Homeobox Protein PITX2
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Intercellular Signaling Peptides and Proteins / genetics*
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Intercellular Signaling Peptides and Proteins / metabolism
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Mice
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Nuclear Proteins / genetics
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Nuclear Proteins / metabolism
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Oligonucleotide Array Sequence Analysis
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Pituitary Neoplasms / blood
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Pituitary Neoplasms / genetics*
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Pituitary Neoplasms / metabolism
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RNA, Messenger / analysis
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RNA, Messenger / metabolism*
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RNA, Neoplasm / analysis
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RNA, Neoplasm / metabolism*
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Transcription Factors
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Transfection
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Triiodothyronine / administration & dosage
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Triiodothyronine / blood
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Triiodothyronine / pharmacology*
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Wnt Proteins
Substances
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Homeodomain Proteins
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Intercellular Signaling Peptides and Proteins
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Nuclear Proteins
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RNA, Messenger
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RNA, Neoplasm
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Transcription Factors
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Wnt Proteins
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Triiodothyronine