Modulation of VEGF/Flk-1 receptor expression in the rat pituitary GH3 cell line by growth factors.
Both vascular endothelial growth factor (VEGF) and its receptor Flk-1 are expressed in normal pituitary cells and in the prolactin- and growth hormone-producing GH3 cell line of the rat, thus suggesting autocrine/paracrine function. Regulation of the Flk-1 receptor system in pituitary cells is poorly understood, but evidence suggests that up-regulated growth factors play a role in its expression and activation. To study the role of growth factors in this process, we examined changes in VEGF and Flk-1 expression in GH3 cells following varied exposure to betaFGF, EGF, and TGFbeta1. Immunofluorescence labelling and laser scanning cytometry were used to measure changes in VEGF and Flk-1 expression. Results showed that betaFGF, EGF and TGFbeta up-regulated the VEGF/FLK-1 receptor system. Distinct patterns of activation were detected. At 2 hours, EGF and TGFbeta caused no significant changes in VEGF and Flk-1 expression; however, betaFGF up-regulated VEGF expression in 99% of cells but only induced modest changes in Flk-1 overexpression. A similar percentage of cells overexpressed VEGF after 24-hour incubation with betaFGF, but more prominent Flk-1 overexpression was detected. At 24 hours, EGF and TGFbeta1 induced a significant increase in both VEGF and Flk-1 expression. In summary, our findings show that VEGF/Flk-1 expression in pituitary cells may be altered by different growth factors. This may affect angiogenesis and the progression of pituitary tumors.
Lombardero
Matilde
M
Division of Pathology, Department of Laboratory Medicine & Pathobiology, St. Michael's Hospital, University of Toronto, Toronto, Ontario, Canada.
Vidal
Sergio
S
Hurta
Robert
R
Román
Alba
A
Kovacs
Kalman
K
Lloyd
Ricardo V
RV
Scheithauer
Bernd W
BW
D000818:Animals; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
D053773:Transforming Growth Factor beta1; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor; D040301:Vascular Endothelial Growth Factor Receptor-2