Insulin-like growth factor-1 and its receptor mediate the autocrine proliferation of human ovarian carcinoma cell lines.
BACKGROUND
IGF-1 regulates the growth of diverse mammalian cell types including several human carcinoma cell lines. The IGF-1 receptor is a glycosylated heterodimer which, upon binding with IGF-1, undergoes tyrosine autophosphorylation. The autophosphorylation of the beta-receptor subunit is a strict requirement for its mitogenic properties.


METHODS
In this study, we have assessed the role of the IGF-1 receptor in the proliferation of ovarian carcinoma cell lines in culture. Effects of anti-sense and sense oligodeoxynucleotides to IGF-1 receptor RNA were tested.


RESULTS
The human ovarian carcinoma cell lines OVCAR-3 and CaOV-3 both grew autonomously in serum-free medium, and their growth was further stimulated by the addition of IGF-1. Incubation of cells with anti-sense oligodeoxynucleotides corresponding to the IGF-1 receptor RNA markedly inhibited cell proliferation both in serum-free medium and in the presence of IGF-1. The inhibition of cell growth by the oligodeoxynucleotides corresponded to a reduction in the amount of detectable phosphorylated IGF-1 receptor.


CONCLUSIONS
The findings indicate that IGF-1 and its specific receptor mediate the autocrine proliferation of human ovarian carcinoma cell lines.
Resnicoff
M
M
Department of Pathology, Jefferson Medical College, Philadelphia, Pennsylvania.
Ambrose
D
D
Coppola
D
D
Rubin
R
R
D000818:Animals; D001483:Base Sequence; D002277:Carcinoma / Q000473:pathology*; D002455:Cell Division; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D051379:Mice; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry; D010051:Ovarian Neoplasms / Q000473:pathology*; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1