Expression and function of platelet-derived growth factors (PDGF) and PDGF receptors in pituitary tumor cell lines

Objective: The growth factors PDGF-AA, PDGF-BB and PDGF-AB regulate through PDGFA and PDGFB receptors the growth, angiogenesis and progression of many types of tumors. In normal and tumoral anterior pituitary, little information is available on the expression and action of PDGF/PDGF receptors. Therefore, we studied the expression and action of this growth factor system in rat anterior pituitary and in a variety of pituitary tumor cell lines (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).

Methods: Expression of PDGF isoforms and PDGF receptors was studied by RT-PCR and/or immunohistochemistry (IHC). Secretion of hormones and VEGF was measured by RIA and ELISA, respectively. Cell proliferation was determined by the WST-assay. Intracellular signaling components were identified by Western/immunoblotting.

Results: By IHC, PDGF receptors were detected in vessel cells in normal rat anterior tissue and PDGF isoforms were only sporadically found in cells not related to the vessels. By RT-PCR, all PDGF isoforms and receptors were found in TtT/GF cells. MtT/S cells expressed PDGF-BB and the 2 types of receptors. In AtT20 cells PDGFA-R and PDGF-BB was found. PDFS cell expressed only PDGFA-R. None of the PDGF forms or receptors was found in GH3 and alphaT3–1 cells. Among PDGF receptor-expressing cells, only the growth of TtT/GF cells was stimulated by PDGF. 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.

Conclusion: Our preliminary studies indicate that the PDGF/PDGF receptor system is differently expressed in normal and tumoral pituitary cells, which needs to be confirmed in human pituitary adenomas.