The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulinlike growth factor 1 with its receptor

Pierluigi Porcu, Andres Ferber, Zbigniew Pietrzkowski, Charles Roberts, Martin Adamo, Derek Leroith, Renato Baserga

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

We have used a plasmid expressing a temperature-sensitive (ts) mutant of simian virus 40 (SV40) T antigen, stably transfected into 3T3 cells, to study the role of insulinlike growth factor 1 (IGF-1) and its receptor in T-antigen-mediated growth. While 3T3 cells do not grow in serum-free medium, in 1% serum, or with the sole addition of either platelet-derived growth factor (PDGF) or IGF-1, cells expressing the tsA. T antigen (BALB 58 cells) grow at 34°C in either PDGF or 1% serum but not in IGF-1. At the restrictive temperature (39.6°C), these cells can only grow in 10% serum. We show that BALB 58 cells, at 34°C, have a markedly increased expression of IGF-1 and IGF-1 mRNA and that their growth in 1% serum (at 34°C) is inhibited by an antisense oligodeoxynucleotide to the IGF-1 receptor RNA. When this tsA plasmid is stably transfected into cells constitutively overexpressing the human IGF-1 receptor cDNA, the resulting cell lines show a constitutively phosphorylated IGF-1 receptor and grow in serum-free medium at 34°C (but not at 39.6°C). A functional SV40 T antigen also increases the expression of a plasmid in which the reporter Iuciferase gene is under the control of a rat IGF-1 promoter. We conclude (i) that the SV40 T antigen induces the expression of IGF-1 and IGF-1 mRNA, at least in part by a transcriptional mechanism, thus altering the growth factors requirements, and (ii) that, in BALB/C3T3 cells, the SV40 T antigen necessitates a functional IGF-1 receptor for its growthstimulating effect in low serum (or PDGF).

Original languageEnglish (US)
Pages (from-to)5069-5077
Number of pages9
JournalMolecular and Cellular Biology
Volume12
Issue number11
StatePublished - Nov 1992
Externally publishedYes

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Simian virus 40
Viral Tumor Antigens
Intercellular Signaling Peptides and Proteins
Growth Factor Receptors
Growth
Platelet-Derived Growth Factor
3T3 Cells
Serum
Plasmids
Serum-Free Culture Media
Messenger RNA
Temperature
Oligodeoxyribonucleotides
Reporter Genes
Complementary DNA
RNA
Cell Line

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulinlike growth factor 1 with its receptor. / Porcu, Pierluigi; Ferber, Andres; Pietrzkowski, Zbigniew; Roberts, Charles; Adamo, Martin; Leroith, Derek; Baserga, Renato.

In: Molecular and Cellular Biology, Vol. 12, No. 11, 11.1992, p. 5069-5077.

Research output: Contribution to journalArticle

Porcu, Pierluigi ; Ferber, Andres ; Pietrzkowski, Zbigniew ; Roberts, Charles ; Adamo, Martin ; Leroith, Derek ; Baserga, Renato. / The growth-stimulatory effect of simian virus 40 T antigen requires the interaction of insulinlike growth factor 1 with its receptor. In: Molecular and Cellular Biology. 1992 ; Vol. 12, No. 11. pp. 5069-5077.
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