J Cell Physiol. 2002 Oct;193(1):64-72. Overexpression of the 18 kDa and 22/24 kDa FGF-2 isoforms results in differential drug resistance and amplification potential. Dini G, Funghini S, Witort E, Magnelli L, Fanti E, Rifkin DB, Del Rosso M. Source Department of Experimental Pathology and Oncology of Florence University, Florence, Italy. gdini@unifi.it Abstract We investigated the role of low molecular weight (LMW) and high molecular weight (HMW) isoforms of basic fibroblast growth factor 2 (FGF-2) in the expression of transformation-related phenotypic alterations, drug sensitivity modulation, and gene amplification potential. For this purpose, we used NIH 3T3 and A31 cells transfected with different cDNA FGF-2 constructs allowing expression of the different proteins. Both cell lines showed marked phenotypic alterations when expressing the LMW FGF-2 or the four HMW FGF-2 isoforms: they acquired a transformed morphology, grew at higher saturation densities in 10% serum, and exhibited anchorage-independent growth and increased invasive potential. However, HMW FGF-2-expressing cells also grew in 1% serum and their invasive potential was lower than in cells expressing all FGF-2 forms or LMW FGF-2 alone. We have grown the different cell lines under a selective pressure of N-(phosphonacetyl)-l-aspartate (PALA), a drug which specifically inhibits the aspartate transcarbamylase activity of the multifunctional carbamyl-P-synthetase/aspartate transcarbamylase/dihydro-orotase genes (CAD) enzyme (and thus inhibits de novo pyrimidine biosynthesis) and selects for cells with amplified copies of the CAD gene. Our results demonstrate that aberrant expression of the LMW FGF-2 and/or HMW FGF-2 isoforms differently modulates drug resistance and gene amplification properties in the NIH 3T3 and A31 cell lines by differential amplification of the CAD gene. Coexpression of all isoforms appears to be necessary to obtain cumulative effects and nuclear-targeted HMW FGF-2 has a pivotal role in such a cooperation. Copyright 2002 Wiley-Liss, Inc. PMID: 12209881 [PubMed - indexed for MEDLINE]

Overexpression of the 18 kDa and 22/24 kDa FGF-2 isoforms results in differential drug resistance and amplification potential / Dini G; Funghini S; Witort E; Magnelli L; Fanti E; Rifkin DB; Del Rosso M. - In: JOURNAL OF CELLULAR PHYSIOLOGY. - ISSN 0021-9541. - STAMPA. - 193:(2002), pp. 64-72. [10.1002/jcp.10152]

Overexpression of the 18 kDa and 22/24 kDa FGF-2 isoforms results in differential drug resistance and amplification potential.

DINI, GERMANA;FUNGHINI, SILVIA;WITORT, EWA JANINA;MAGNELLI, LUCIA;FANTI, ELENA;DEL ROSSO, MARIO
2002

Abstract

J Cell Physiol. 2002 Oct;193(1):64-72. Overexpression of the 18 kDa and 22/24 kDa FGF-2 isoforms results in differential drug resistance and amplification potential. Dini G, Funghini S, Witort E, Magnelli L, Fanti E, Rifkin DB, Del Rosso M. Source Department of Experimental Pathology and Oncology of Florence University, Florence, Italy. gdini@unifi.it Abstract We investigated the role of low molecular weight (LMW) and high molecular weight (HMW) isoforms of basic fibroblast growth factor 2 (FGF-2) in the expression of transformation-related phenotypic alterations, drug sensitivity modulation, and gene amplification potential. For this purpose, we used NIH 3T3 and A31 cells transfected with different cDNA FGF-2 constructs allowing expression of the different proteins. Both cell lines showed marked phenotypic alterations when expressing the LMW FGF-2 or the four HMW FGF-2 isoforms: they acquired a transformed morphology, grew at higher saturation densities in 10% serum, and exhibited anchorage-independent growth and increased invasive potential. However, HMW FGF-2-expressing cells also grew in 1% serum and their invasive potential was lower than in cells expressing all FGF-2 forms or LMW FGF-2 alone. We have grown the different cell lines under a selective pressure of N-(phosphonacetyl)-l-aspartate (PALA), a drug which specifically inhibits the aspartate transcarbamylase activity of the multifunctional carbamyl-P-synthetase/aspartate transcarbamylase/dihydro-orotase genes (CAD) enzyme (and thus inhibits de novo pyrimidine biosynthesis) and selects for cells with amplified copies of the CAD gene. Our results demonstrate that aberrant expression of the LMW FGF-2 and/or HMW FGF-2 isoforms differently modulates drug resistance and gene amplification properties in the NIH 3T3 and A31 cell lines by differential amplification of the CAD gene. Coexpression of all isoforms appears to be necessary to obtain cumulative effects and nuclear-targeted HMW FGF-2 has a pivotal role in such a cooperation. Copyright 2002 Wiley-Liss, Inc. PMID: 12209881 [PubMed - indexed for MEDLINE]
2002
193
64
72
Dini G; Funghini S; Witort E; Magnelli L; Fanti E; Rifkin DB; Del Rosso M
File in questo prodotto:
File Dimensione Formato  
Overexpression of the 18 kDa and 22:24 kDa FGF-2 isoforms results in differential drug resistance and amplification potential..pdf

Accesso chiuso

Tipologia: Versione finale referata (Postprint, Accepted manuscript)
Licenza: Tutti i diritti riservati
Dimensione 275.7 kB
Formato Adobe PDF
275.7 kB Adobe PDF   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/344855
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 19
  • ???jsp.display-item.citation.isi??? 16
social impact