Characterization of tumors produced by signal peptide-basic fibroblast growth factor-transformed cells.
Basic fibroblast growth factor (bFGF) is found in a variety of cells and tissues. We have previously shown that bFGF is a transforming growth factor, but only when fused to a signal peptide (sp-bFGF). Cells expressing the native bFGF are tumorigenic in nude mice only, where the tumors form at a low frequency and grow very slowly as compared to sp-bFGF tumors. The cells transformed by the sp-bFGF growth factor gene cause rapidly growing tumors within 10 days in 100% of syngeneic and nude mice. In nude mice, the tumors are highly vascularized, while the vascularization in immunocompetent syngeneic mice is not as prominent. The syngeneic mice have a characteristic humoral immune response to sp-bFGF tumors, which differs from that mounted against ras-induced tumors. The ability of bFGF to induce tumorigenicity is significant in view of the recent discoveries of three new oncogenes: hst, int-2, and an oncogene from a human colon cancer. In addition to homology with FGF, the proteins encoded by these oncogenes all have a potential signal peptide at the protein's amino terminus, suggesting a mode of action analogous to that of our artificial signal peptide-bFGF (sp-bFGF) transforming growth factor model system.
Rogelj
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Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142.
Weinberg
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Fanning
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Klagsbrun
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D000818:Animals; D000917:Antibody Formation; D002461:Cell Line, Transformed; D005346:Fibroblast Growth Factors / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000276:immunology / Q000473:pathology*; D009389:Neovascularization, Pathologic; D009857:Oncogenes; D021382:Protein Sorting Signals / Q000502:physiology*
D021382:Protein Sorting Signals; D005346:Fibroblast Growth Factors