The role of the Bcl-3 proto-oncogene in thyroid hormone-induced liver cell proliferation.
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.
Malik
Raza
R
Centre for Hepatology, Department of Medicine, Royal Free Campus, Royal Free and University College Medical School, Hampstead, London, UK. r.malik@medsch.ucl.ac.uk
Bungay
Anton
A
Sadiq
Amama
A
Brown
David
D
Riemann
Marc
M
Choudhury
Sarah
S
Schmid
Roland
R
Selden
Clare
C
Hodgson
Humphrey
H
D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D049109:Cell Proliferation / Q000187:drug effects*; D005786:Gene Expression Regulation; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014284:Triiodothyronine / Q000494:pharmacology*
D000081242:B-Cell Lymphoma 3 Protein; C000631345:Bcl3 protein, mouse; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D014284:Triiodothyronine