N-myc oncogene enhances mitogenic responsiveness of diploid human fibroblasts to growth factors but fails to immortalize.
The N-myc gene is amplified in several types of human tumors. To assess the role of the N-myc gene in the transformation of normal human cells, we transfected an N-myc expression vector into diploid human fibroblasts. Transfected clones were isolated and found to express the N-myc gene at levels similar to those seen in a tumor cell line (neuroblastoma LA-N-1) which contains an amplified N-myc gene. The level of N-myc expression decreased as the N-myc clones senesced. Clones expressing N-myc had an increased saturation density and an altered morphology but did not have an extended lifespan. Under low serum conditions, neither the clones expressing N-myc nor the control cells showed anchorage-dependent growth. Clones expressing N-myc were compared to control cells to determine if different growth factors would affect the ability of cells to grow in soft agarose. Clones expressing N-myc and the control cells did not grow in soft agarose supplemented with epidermal growth factor (EGF) or transforming growth factor-alpha (TGF-alpha). However, compared to control cells, clones expressing N-myc grew in agarose 2.8- to 18-fold higher in response to basic fibroblast growth factor (bFGF) and 5.5- to 55-fold higher in response to platelet-derived growth factor B-chain homodimer (PDGF-BB).
Brondyk
W H
WH
McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706.
Boeckman
F A
FA
Fahl
W E
WE
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004171:Diploidy; D004815:Epidermal Growth Factor / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D015870:Gene Expression; D016259:Genes, myc / Q000235:genetics*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000209:etiology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011518:Proto-Oncogene Proteins / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D014162:Transfection; D016211:Transforming Growth Factor alpha / Q000494:pharmacology
D006133:Growth Substances; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D016211:Transforming Growth Factor alpha; D016222:Fibroblast Growth Factor 2; D004815:Epidermal Growth Factor