The role of the Bcl-3 proto-oncogene in thyroid hormone-induced liver cell proliferation

Artif Organs. 2009 Jun;33(6):425-30. doi: 10.1111/j.1525-1594.2009.00752.x.

Abstract

The aim of the study was to determine if thyroid hormone-induced liver cell proliferation occurs through the Bcl-3 proto-oncogene. Rodents (including Bcl-3 knockout mice and the wild-type strain) were injected with a single dose of tri-iodothyronine (T(3)) and sacrificed at various time points. Hepatic mRNA (real-time polymerase chain reaction ) and protein expression (Western analysis) of Bcl-3 was quantified in rats stimulated with T(3). Cell proliferation was induced in a variety of cell types after T(3) injection at 24 h including hepatocytes (7 +/- 1.1% vs. 0.45 +/- 0.025%; P < 0.01), hepatic nonparenchymal cells (3.8 +/- 1.2% vs. 0.3 +/- 0.01%; P < 0.01), renal tubular cells (8.1 +/- 1.6% vs. 0.2 +/- 0.035%; P < 0.01), and splenic lymphocytes (4.8 +/- 1.2% vs. 0.35 +/- 0.02%; P < 0.01). We showed a twofold increase in hepatic Bcl-3 mRNA (P < 0.01) and protein expression (P < 0.01) at 24 h in rats stimulated with T(3). However, there were no differences in the rate of liver cell proliferation between Bcl-3 knockout mice and the wild-type strain (0.4 +/- 0.15% vs. 0.3 +/- 0.1%), indicating that Bcl-3 was not functionally involved in thyroid hormone-induced liver cell proliferation. A single gene is unlikely to initiate the process of thyroid hormone-induced cell proliferation. A complex interaction between the genomic and nongenomic effects of thyroid hormone is likely to regulate the mitogenic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Lymphoma 3 Protein
  • Cell Proliferation / drug effects*
  • Gene Expression Regulation
  • Liver / cytology*
  • Liver / metabolism
  • Mice
  • Mice, Knockout
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*
  • Triiodothyronine / pharmacology*

Substances

  • B-Cell Lymphoma 3 Protein
  • Bcl3 protein, mouse
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • Transcription Factors
  • Triiodothyronine