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.

Experimental Design: 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.