Downregulation of cyclin G2 by insulin, insulin-like growth factor I (IGF-I) and AspB10 insulin (X10): role in mitogenesis

The mechanisms whereby insulin analogues may cause enhanced mitogenicity through activation of either the insulin receptor (IR) or the IGF-I receptor (IGF-IR) are incompletely understood. We demonstrate that in L6 myoblasts expressing only IGF-IRs as well as in the same cells overexpressing the IR, IGF-I, insulin, and AspB10 insulin (X10) downregulate the mRNA expression level of the cell cycle inhibitor cyclin G2, as measured by qRT-PCR, and induce cell growth measured by [6-3H] thymidine incorporation into DNA. Western blotting showed a marked downregulation of cyclin G2 at the protein level in both cell lines. Overexpression of cyclin G2 in the two cell lines diminished the mitogenic effect of all three ligands. The use of specific inhibitors indicated that both the MAPK and the PI3K pathways mediate the downregulation of Ccng2. The downregulation of CCNG2 by the three ligands was also observed in other cell lines: MCF-7, HMEC, Saos-2, R-/IR, and INS-1. These results indicate that regulation of cyclin G2 is a key mechanism whereby insulin, insulin analogues and IGF-I stimulate cell proliferation.
Source: BJ Gene - Category: Biochemistry Authors: Tags: BJ Signal Source Type: research