Aberrant expression of basic fibroblast growth factor in NIH-3T3 cells alters drug resistance and gene amplification potential.
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.
Huang
A
A
Manitoba Institute of Cell Biology, University of Manitoba, Winnipeg, Canada.
Jin
H
H
Wright
J A
JA
D016475:3T3 Cells; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004351:Drug Resistance / Q000235:genetics; D016222:Fibroblast Growth Factor 2 / Q000096:biosynthesis* / Q000235:genetics; D005784:Gene Amplification; D051379:Mice; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection
D016222:Fibroblast Growth Factor 2; D001224:Aspartic Acid; C013195:sparfosic acid; D010746:Phosphonoacetic Acid