Growth arrest of thyrotropic tumors by thyroid hormone is correlated with novel changes in Wnt-10A.
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.
Kerr
Janice M
JM
University of Colorado Health Sciences Center, Department of Medicine, Division of Endocrinology, Metabolism, and Diabetes, MS8106, P.O. Box 6511 Denver, CO 80262, USA. janice.kerr@uchsc.edu
Gordon
David F
DF
Woodmansee
Whitney W
WW
Sarapura
Virginia D
VD
Ridgway
E Chester
EC
Wood
William M
WM
D000818:Animals; D045744:Cell Line, Tumor / Q000187:drug effects; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D018816:Genes, cdc / Q000187:drug effects; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010911:Pituitary Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000032:analysis / Q000378:metabolism*; D014157:Transcription Factors; D014162:Transfection; D014284:Triiodothyronine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051153:Wnt Proteins; D000097577:Homeobox Protein PITX2
D018398:Homeodomain Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; D014284:Triiodothyronine; D051153:Wnt Proteins; D000097577:Homeobox Protein PITX2