CELL CYCLE MODULATION BY PARATHYROID HORMONE IN HUMAN COLON ADENOCARCINOMA CELLS

Parathyroid hormone (PTH) is a major mediator of bone remodeling and acts as a key regulator of calcium homeostasis. Depending on the cellular context, PTH may also stimulate or inhibit apoptosis and induce alterations in cell cycle regulation. Previously we found that in Caco-2 cells, a cell line derived from human colon adenocarcinoma, the hormone (10-8 M) in the absence of serum is pro-apoptotic and with low dose of serum has anti-proliferative effect increasing the protein expression of cell cycle inhibitor p27Kip1 and decreasing the expression of cyclins D1 and D3 and cyclindependent kinase CDK6. In this work we further studied the molecular mechanisms that mediate the response to PTH in Caco-2 cells cultured without serum. We evidenced that, in the absence of serum, PTH receptor type 1 (PTHR1) is located exclusively in the nucleus. Moreover, the hormone at 10-8 M decreases the number of living cells and no changes were observed at lower concentrations. Even more, only the protein expression of cell cycle inhibitory p15INK4B is modified by the hormone in the absence of serum. These results suggest that PTH at a dose of 10-8 M arrest cell cycle progression in Caco-2 cells; however, according to the experimental conditions, this effect would be mediated by different cell cycle associated proteins.