Involvement of ERK1/2, p38 MAPK and PI3K/Akt signaling pathways in the regulation of cell cycle progression by PTHrP in colon adenocarcinoma cells

CALVO, NATALIA; MARTIN MARIA JULIA; RUSSO DE BOLAND ANA; GENTILI, CLAUDIA

BIOCHEMISTRY AND CELL BIOLOGY

NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS

Lugar: Otawa; Año: 2014 vol. 92 p. 305 - 315

0829-8211

Parathyroid Hormone-related Peptide (PTHrP) is distributed in most fetal and adult tissues and its expression correlates with the severity of colon carcinoma. Recently we obtained evidence that in Caco-2 cells, a cell line from human colorectal adenocarcinoma, exogenous PTHrP increases the number of live cells, via ERK1/2, p38 MAPK and PI3-kinase and induces the expression of cyclin D1, a cell cycle-regulatory protein. In this study, we further investigated the role of PTHrP in the regulation of the cell cycle progression in these intestinal cells. Flow cytometry analysis revealed that PTHrP treatment diminishes the number of cells in the G0/G1 phase and increases the number in both, S and G2/M phases. The hormone increases the expression of CDK6 and diminishes the amount of negative cell cycle regulators p27Kip1, p15INK4B and p53. However, PTHrP does not modify the expression of cyclin D3, CDK4 and p16INK4A. In addition, inhibitors of ERK1/2 (PD98059), p38 MAPK (SB203580) and PI3Kinase (LY294002) reversed PTHrP response in Caco-2 cells. Taken together, our results suggest that PTHrP positively modulates cell cycle progression and changes the expression of proteins involved in cell cycle regulation via ERK1/2, p38 MAPK and PI3K signaling pathways in Caco-2 cells.