Growth arrest of thyrotropic tumors by thyroid hormone is correlated with novel changes in Wnt-10A

Mol Cell Endocrinol. 2005 Jun 30;238(1-2):57-67. doi: 10.1016/j.mce.2005.03.004.

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

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line, Tumor / drug effects
  • Down-Regulation
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Genes, cdc / drug effects
  • Homeobox Protein PITX2
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Pituitary Neoplasms / blood
  • Pituitary Neoplasms / genetics*
  • Pituitary Neoplasms / metabolism
  • RNA, Messenger / analysis
  • RNA, Messenger / metabolism*
  • RNA, Neoplasm / analysis
  • RNA, Neoplasm / metabolism*
  • Transcription Factors
  • Transfection
  • Triiodothyronine / administration & dosage
  • Triiodothyronine / blood
  • Triiodothyronine / pharmacology*
  • Wnt Proteins

Substances

  • Homeodomain Proteins
  • Intercellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Transcription Factors
  • Wnt Proteins
  • Triiodothyronine