Abstract
The insulin-like growth factors (IGF-I and IGF-II) participate in the control of cell proliferation in normal and neoplastic lung cells. To examine the role of IGF binding proteins (IGFBPs) in modulating IGF actions in lung, we examined the production and regulation of IGFBPs from A549 cells, a human adenocarcinoma-derived lung cell line. Ligand blot and immunoblot analysis of conditioned media (CM) from A549 cells demonstrated IGFBP bands of relative molecular mass (M(r)) approximately 39-43,000 (IGFBP-3), 34,000 (IGFBP-2), 30,000 (IGFBP-1), and 24,000 (IGFBP-4). IGFBP-3 abundance in A549 cell CM increased following exposure to IGF-I and IGF-II (3.0- and 1.8-fold, respectively) without a change in IGFBP-3 transcript abundance, suggesting IGFBP-3 is post-transcriptionally regulated. Cycloheximide almost completely abrogated the IGF-I-stimulated increase in CM IGFBP-3, suggesting that ongoing protein synthesis is necessary for the IGF-I-stimulated increase in IGFBP-3 abundance. Increases in IGFBP-3 occurred by at least two mechanisms, through activation of the type 1 IGF receptor and by a type 1 IGF receptor independent mechanism. The increase in IGFBP-3 was due, in part, to activation of the type 1 IGF receptor because blocking...Continue Reading
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