Aberrant expression of basic fibroblast growth factor in NIH-3T3 cells alters drug resistance and gene amplification potential

Exp Cell Res. 1994 Aug;213(2):335-9. doi: 10.1006/excr.1994.1207.


We have investigated the genetic stability of NIH-3T3 cells transfected with sequences coding for basic fibroblast growth factor (bFGF) by determining drug resistance and gene amplification potential. Colony-forming experiments and fluctuation analyses showed that the frequency and rate of resistance to N-(phosphonacetyl)-L-aspartate (PALA) was dramatically elevated in cells transfected with either the normal bFGF coding sequence that lacks a known signal for secretion or a chimeric bFGF sequence that targets the growth factor to the secretory pathway. Basic FGF-transfected cells that grew in the presence of PALA were found to possess an amplification of the CAD gene, which codes for a multifunctional protein involved in pyrimidine biosynthesis and is the site of action for PALA. The observation that these alterations occur in cells transfected with a bFGF sequence, without a conventional signal sequence for secretion, suggests an intracrine as opposed to autocrine mechanism of action. The results describe a new function for this growth factor and suggest a novel role for aberrant expression of bFGF in mechanisms of tumor progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / pharmacology
  • Drug Resistance / genetics
  • Fibroblast Growth Factor 2 / biosynthesis*
  • Fibroblast Growth Factor 2 / genetics
  • Gene Amplification
  • Mice
  • Phosphonoacetic Acid / analogs & derivatives
  • Phosphonoacetic Acid / pharmacology
  • Transfection


  • Fibroblast Growth Factor 2
  • Aspartic Acid
  • sparfosic acid
  • Phosphonoacetic Acid