Antagonistic effect of PDGF and NGF on transcription of ribosomal DNA and tumor cell proliferation.
The molecular mechanism by which NGF and PDGF affect growth of tumor cells was tested in human melanoma WM 266-4 and colorectal carcinoma SW 707 cell lines. We present evidence that NGF translocated to the nucleus and bound to the chromatin of SW 707 cells, which express the cell surface and the chromatin receptor for NGF, inhibits ribosomal RNA synthesis which in consequence leads to inhibition of cell proliferation. In WM 266-4 cells, which do not express NGF receptor, NGF does not affect cell proliferation. In contrast, PDGF translocated to the nucleus of both SW 707 and WM 266-4 cells activates ribosomal RNA synthesis. We report here that NGF abolishes PDGF-activated ribosomal RNA synthesis and PDGF-stimulated growth of tumor cells.
Wistar Institute of Anatomy and Biology, Philadelphia, Pennsylvania 19104.
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Rakowicz-Szulczynska
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Koprowski
D002455:Cell Division / Q000187:drug effects*; D002843:Chromatin / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D008545:Melanoma / Q000473:pathology*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D012335:RNA, Ribosomal / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D002843:Chromatin; D004275:DNA, Ribosomal; D009414:Nerve Growth Factors; D010982:Platelet-Derived Growth Factor; D012335:RNA, Ribosomal