Platelet-derived growth factor (PDGF) and PDGF receptor expression and function in pituitary tumor cell lines

PDGF-A and PDGF-B chains are involved through PDGFA and PDGFB receptors in the progression of many types of tumors by stimulating tumor cell growth and/or angiogenesis. Imatinib mesylate (Gleevec), an inhibitor of the PDGF signaling cascade, is clinically used with variable success in the treatment of different types of cancer. Since little information is available on the expression and action of PDGF/PDGF receptors in normal and adenomatous pituitary, we studied the expression and action of this growth factor system in a variety of pituitary tumor cell lines. Studies were performed with lactosomatotroph rat GH3 cells, somatotroph rat MtT/S cells, folliculostellate mouse TtT/GF cells, corticotroph mouse AtT20 cells, gonadotroph mouse alphaT3–1 cells, and folliculostellate human PDFS cells. By RT-PCR, all PDGF chains and receptors were found in TtT/GF cells. MtT/S cells expressed PDGF-B and the 2 types of receptors. In AtT20 cells PDGFA-R and PDGF-B was found. PDFS cell expressed only PDGFA-R and none of the PDGF chains or receptors was found in GH3 and alphaT3–1 cells. In cells expressing PDGF receptors, PDGF stimulated only growth of TtT/GF cells. Secretion of vascular endothelial growth factor (VEGF) was strongly enhanced by PDGF in TtT/GF cells whereas ACTH production was not affected in AtT20 cells. In studies on the mechanism of action, preliminary experiments in TtT/GF cells showed phosphorylation of PDK1, PTEN and Akt(Ser473) signaling components in response to PDGF. Our preliminary studies indicate that in part of pituitary adenomas a functional PDGF/PDGF receptor system may exist, which needs to be confirmed in future investigations.