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

STERLE HA; VALLI E; CAYROL MF; PAULAZO MA; MARTINELL LAMAS D; DIAZ FLAQUE MC; KLECHA AJ; COLOMBO L; MEDINA V; CREMASCHI GA; BARREIRO ARCOS ML

JOURNAL OF ENDOCRINOLOGY

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2014

0022-0795

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. Here, 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 were inoculated with EL-4 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 the tumor cells with CFSE. Additionally, the hyperthyroid mice exhibited reduced survival. The hypothyroid mice were not significantly different from the euthyroid controls in these parameters. Additionally, only tumors from the hyperthyroid animals had increased expression levels of PCNA and active caspase 3. Also, the differential expression of cell cycle regulatory proteins was observed. The levels of cyclins D1 and D3 were augmented in the tumors of the hyperthyroid animals, whereas the cell cycle inhibitors p16/INK4A and p27/Kip1 and the tumor suppressor p53 were increased in the hypothyroid mice. Intratumoral and peritumoral vasculogenesis was increased only in the hyperthyroid mice. Therefore, we propose that the thyroid status modulates the in vivo growth of EL-4 T lymphoma through of the regulation of cyclin, cyclin-dependent kinase inhibitor, and tumor suppressor gene expression, as well as the stimulation of angiogenesis.