Overexpression of platelet-derived growth factor B and downregulation of PDGF-receptor alpha in human immortalized fibroblasts.
Since immortalization of cells is critical in multistep carcinogenesis, efforts should be made to elucidate the mechanisms of the immortalization. To determine whether platelet-derived growth factor (PDGF) signal pathways play a role in immortalization of cells, we compared mRNA expressions of PDGFs and their receptors in three immortalized human fibroblast cell lines (SUSM-1, OUMS-24F, and KMST-6) with their normal parent cells. As a result, mRNA expression of PDGF-B (oncogene: c-sis) was upregulated in these immortalized cells. Unexpectedly, the expression of alpha- and beta-PDGF receptor genes was downregulated. PDGFR-alpha mRNA was remarkably decreased. When exogenous PDGFR-alpha was expressed transiently in the KMST-6 cells, the morphology of the cells resembled that of normal cells. These results suggest that the overexpression of PDGF-B (c-sis) and downregulation of PDGFR-alpha are related to the phenotypic characteristics of immortalized human cells.
Department of Cell Biology, Institute of Cellular and Molecular Biology, Okayama University Medical School, 2-5-1 Shikata, Okayama 700-8558, Japan.
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C
Gao
M
M
Miyazaki
T
T
Kondo
T
T
Tsuji
M
M
Sakaguchi
M
M
Namba
D015152:Blotting, Northern; D002478:Cells, Cultured / Q000166:cytology; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D020574:Proto-Oncogene Proteins c-sis / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000096:biosynthesis*; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D020796:Receptor, Platelet-Derived Growth Factor alpha; D017479:Receptors, Platelet-Derived Growth Factor