Thyroid status modulates T lymphoma growth via cell cycle regulatory proteins and angiogenesis.

Abstract

We have shown in vitro that thyroid hormones (THs) regulate the balance between proliferation and apoptosis of T lymphoma cells. The effects of THs on tumor development have been studied, but the results are still controversial. Herein, we show the modulatory action of thyroid status on the in vivo growth of T lymphoma cells. For this purpose, euthyroid, hypothyroid, and hyperthyroid mice received inoculations of EL4 cells to allow the development of solid tumors. Tumors in the hyperthyroid animals exhibited a higher growth rate, as evidenced by the early appearance of palpable solid tumors and the increased tumor volume. These results are consistent with the rate of cell division determined by staining tumor cells with carboxyfluorescein succinimidyl ester. Additionally, hyperthyroid mice exhibited reduced survival. Hypothyroid mice did not differ significantly from the euthyroid controls with respect to these parameters. Additionally, only tumors from hyperthyroid animals had increased expression levels of proliferating cell nuclear antigen and active caspase 3. Differential expression of cell cycle regulatory proteins was also observed. The levels of cyclins D1 and D3 were augmented in the tumors of the hyperthyroid animals, whereas the cell cycle inhibitors p16/INK4A (CDKN2A) and p27/Kip1 (CDKN1B) and the tumor suppressor p53 (TRP53) were increased in hypothyroid mice. Intratumoral and peritumoral vasculogenesis was increased only in hyperthyroid mice. Therefore, we propose that the thyroid status modulates the in vivo growth of EL4 T lymphoma through the regulation of cyclin, cyclin-dependent kinase inhibitor, and tumor suppressor gene expression, as well as the stimulation of angiogenesis.

• Authors: H A Sterle, E Valli, F Cayrol, M A Paulazo, D J Martinel Lamas, M C Diaz Flaqué, A J Klecha, L Colombo, V A Medina, G A Cremaschi, M L Barreiro Arcos
• Journal: The Journal of endocrinology (J Endocrinol) Vol. 222 Issue 2 Pg. 243-55 (Aug 2014) ISSN: 1479-6805 [Electronic] England
• PMID: 24928937 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Society for Endocrinology.

Chemical References

• Cell Cycle Proteins
• Cyclin-Dependent Kinase Inhibitor p21
• Proliferating Cell Nuclear Antigen
• Tumor Suppressor Protein p53
• Cyclin D1
• Cyclin-Dependent Kinase Inhibitor p27
• Casp3 protein, mouse
• Caspase 3

Topics

• Animals
• Apoptosis
• Caspase 3 (biosynthesis)
• Cell Cycle Proteins (biosynthesis)
• Cell Line, Tumor
• Cell Proliferation
• Cyclin D1 (biosynthesis)
• Cyclin-Dependent Kinase Inhibitor p21 (biosynthesis)
• Cyclin-Dependent Kinase Inhibitor p27 (biosynthesis)
• Female
• Hyperthyroidism (complications, physiopathology)
• Hypothyroidism (complications, physiopathology)
• Lymphoma, T-Cell (pathology, physiopathology)
• Mice
• Mice, Inbred C57BL
• Neoplasm Transplantation
• Neovascularization, Pathologic
• Proliferating Cell Nuclear Antigen (biosynthesis, metabolism)
• Thyroid Gland (physiology)
• Tumor Suppressor Protein p53 (biosynthesis)