Role of PTH and PTHrP in the regulation of cell cycle in colon adenocarcinoma cells

CALVO N; GENTILI C; RUSSO DE BOLAND A

Puerto Madryn, Chubut

Congreso; XLVI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2010

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB)

Parathyroid hormone (PTH) functions as a major mediator of bone remodeling and as an essential regulator of calcium homeostasis. Parathyroid hormone-related protein (PTHrP) was initially identified through its role in humoral hypercalcemia of malignancy and is able to interact with PTH receptor type 1. In this study, we investigated the role of PTH and PTHrP in the regulation of the cell cycle in human Caco-2 intestinal cells. First, the nuclei were stained with propidium iodide and the DNA content was measured using a flow cytometer. The results revealed that PTH treatment (10-8 M, 24 h) increases the number of G0/G1 phase cells and diminishes the number of S phase cells respect to control. In addition, analysis by western blot showed that the hormone induces the expression of the inhibitory proteins p27 and p15 and diminishes the expression of cyclin D1 and D3. However, the amount of p21 was not different in the absence or presence of PTH. By contrast, and although they share the same receptor, there was no change in the expression of these proteins after exposure of Caco-2 cells to PTHrP (10-8 M). Taken together, our results suggest that PTH induces changes in the expression of proteins involved in cell cycle regulation and produces G0/G1 phase arrest of Caco-2 intestinal cells.