title: Rosiglitazone inhibits adrenocortical cancer cell proliferation by interfering with the IGF-IR intracellular signaling.
abstract: Rosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-gamma, has been recently described as possessing antitumoral properties. We investigated RGZ effect on cell proliferation in two cell line models (SW13 and H295R) of human adrenocortical carcinoma (ACC) and its interaction with the signaling pathways of the activated IGF-I receptor (IGF-IR). We demonstrate a high expression of IGF-IR in the two cell lines and in ACC. Cell proliferation is stimulated by IGF-I in a dose- and time-dependent manner and is inhibited by RGZ. The analysis of the main intracellular signaling pathways downstream of the activated IGF-IR, phosphatidyl inositol 3-kinase (PI3K)-Akt, and extracellular signal-regulated kinase (ERK1/2) cascades reveals that RGZ rapidly interferes with the Akt and ERK1/2 phosphorylation/activation which mediates IGF-I stimulated proliferation. In conclusion, our results suggest that RGZ exerts an inhibitory effect on human ACC cell proliferation by interfering with the PI3K/Akt and ERK1/2 signaling pathways downstream of the activated IGF-IR.
authors.affiliation: Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Cantini
authors.forename: Adriana
authors.initials: A
authors.lastname: Lombardi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Piscitelli
authors.forename: Giada
authors.initials: G
authors.lastname: Poli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ceni
authors.forename: Sara
authors.initials: S
authors.lastname: Marchiani
authors.forename: Tonino
authors.initials: T
authors.lastname: Ercolino
authors.forename: Andrea
authors.initials: A
authors.lastname: Galli
authors.forename: Mario
authors.initials: M
authors.lastname: Serio
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.forename: Michaela
authors.initials: M
authors.lastname: Luconi