Journal
JOURNAL OF ENDOCRINOLOGY
Volume 222, Issue 2, Pages 243-255Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-14-0159
Keywords
thyroid hormones; T lymphoma; cell cycle; angiogenesis
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Funding
- Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET)
- Proyectos de Investigacion Plurianuales (PIP)-CONICET [00275]
- Agencia Nacional para la Promocion Cientifica y Tecnica
- Proyectos de Investigacion Cientifica y Tecnologica (PICT) [1858]
- PICT Raices [1328]
- Secretaria de Ciencia y Tecnica Universidad de Buenos Aires, (UBACYT) [20020100100291]
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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 havebeen studied, but the results are still controversial. Herein, weshowthemodulatory 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 consistentwiththe rate of cell division determined by stainingtumor cellswith carboxyfluorescein succinimidyl ester. Additionally, hyperthyroid mice exhibited reduced survival. Hypothyroid mice did not differ significantly fromthe 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 increasedinhypothyroidmice. Intratumoral andperitumoral vasculogenesiswas increasedonly 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.
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