Platelet-derived growth factor-induced expression of messenger RNA for the proliferating cell nuclear antigen requires a functional receptor for the insulin-like growth factor I.
Stimulation of quiescent fibroblasts or fibroblast-like cells with growth factors causes a sharp increase in the mRNA levels of several DNA synthesis genes. With most of these genes, the increase in mRNA levels requires at least 2 growth factors [usually platelet-derived growth factor (PDGF) and insulin-like growth factor-I (IGF-I)], but the mRNA of the proliferating cell nuclear antigen (PCNA) gene is induced by PDGF only. Since PDGF is known to induce also expression of IGF-I and its receptor, we inquired as to whether the PCNA mRNA induction by PDGF depended on a functional IGF autocrine loop. Using R- cells, i.e., mouse embryo cells in which the IGF-I receptor genes have been disrupted by homologous recombination, we show here that the functional integrity of the IGF-I receptor is obligatory for the PDGF-induced increase in PCNA mRNA levels. However, PCNA pre-mRNA levels are increased by PDGF even in the absence of the IGF-I receptor. These experiments confirm the importance of the IGF-I receptor in the control of cellular proliferation in animal cells, and suggest that one of its functions may be in the processing of certain pre-mRNAs required for orderly cell cycle progression.
Miura
M
M
Jefferson Cancer Institute, Thomas Jefferson University, Philadelphia, Pennsylvania 19107.
Li
S W
SW
Dumenil
G
G
Baserga
R
R
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D006207:Half-Life; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000096:biosynthesis*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger / Q000096:biosynthesis*; D017526:Receptor, IGF Type 1 / Q000378:metabolism*
D009687:Nuclear Proteins; D010982:Platelet-Derived Growth Factor; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1