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The Role of the Bcl‐3 Proto‐Oncogene in Thyroid Hormone‐Induced Liver Cell Proliferation
Author(s) -
Malik Raza,
Bungay Anton,
Sadiq Amama,
Brown David,
Riemann Marc,
Choudhury Sarah,
Schmid Roland,
Selden Clare,
Hodgson Humphrey
Publication year - 2009
Publication title -
artificial organs
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.684
H-Index - 76
eISSN - 1525-1594
pISSN - 0160-564X
DOI - 10.1111/j.1525-1594.2009.00752.x
Subject(s) - medicine , endocrinology , thyroid , cell growth , hormone , oncogene , thyroid hormone receptor , cell , biology , chemistry , cell cycle , biochemistry
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.