European review for medical and pharmacological sciences

Glial cell line-derived neurotrophic factor promotes proliferation of neuroglioma cells by up-regulation of cyclins PCNA and Ki-67.

PMID 26125271


We wished to test whether glial cell line-derived neurotrophic factor (GDNF) stimulates proliferation of gliomas by up-regulating expression of nuclear cyclins PCNA and Ki37. As a model, we tested rat C6 glioma cell line exposed to basal conditions, vehicle control, or exogenous GDNF at different concentrations (0-90 µg/L) or different times (0-72 hours). Cell proliferation was quantified by MTT test, cell cycle by flow cytometry and propidium iodide staining, expression of PCNA and Ki67 by intracellular antibody staining and flow cytometry. We first observed that cell proliferation was most stimulated by GDNF at concentration of 70 µg/L and incubation time of 48 hours. Using this concentration and incubation time, we next documented that GDNF increased the percentage of cells in the S phase (47.98% vs. 32.57% in basal cells; p < 0.05), while not affecting the percentage of cells in G0/G1 or G2/M phases. Finally, we demonstrated that expression of both PCNA and Ki67 was significantly increased in cells exposed to GDNF. We demonstrate that GDNF stimulates proliferation of glioma cells by up-regulating expression of cyclins PCNA and Ki-67.