Fibroblast growth factor 3 is tumorigenic for mouse mammary cells orthotopically implanted in nude mice.
Fibroblast growth factor-3 (Fgf-3) is involved in mouse mammary tumorigenesis since the Fgf-3 gene is a main target for mouse mammary tumor virus (MMTV) insertional activation. Its action has been correlated with the appearance of pregnancy-dependent tumors. We describe here the effects on normal mouse mammary EF43 cells of the short Fgf-3 protein form which enters the secretory pathway. The genes, Fgf-3 AUG or Fgf-4 for comparison, were introduced in the mammary cells by means of retroviral vectors. Fgf-3 expression did not modify EF43 cell morphology, had no effect on growth in soft agar nor on the inhibitory action exerted on cell growth by TGF-beta 1; however, it allowed the cells to grow under low serum conditions in the absence of insulin and EGF. The Fgf-3-expressing cells were not tumorigenic in nude mice when injected s.c., but tumors developed when the cells were implanted in the mammary gland. The tumors appeared after some latency; they had a slow growth phase followed by a phase of increased growth rate. An identical tumoral growth pattern was observed in ovariectomized nude mice. These results show that the secreted Fgf-3 form can initiate tumorigenesis and that the induced tumors are hormone-independent. The mammary-gland environment, however, is required for the EF43 cells to grow and differentiate. During that process, which resembles natural cell growth during mammary-gland development at pregnancy, the cells could pass through a stage which is specifically sensitive to Fgf-3.
Hajitou
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Laboratory of Fundamental Virology, University of Liège, Belgium.
Calberg-Bacq
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CM
D016475:3T3 Cells; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D017690:Cell Transplantation; D004285:Dogs; D005260:Female; D051518:Fibroblast Growth Factor 3; D005346:Fibroblast Growth Factors / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D008321:Mammary Glands, Animal / Q000166:cytology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics*; D051379:Mice; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D014162:Transfection
C489197:Fgf3 protein, mouse; D051518:Fibroblast Growth Factor 3; D011518:Proto-Oncogene Proteins; D005346:Fibroblast Growth Factors