Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling
Rosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-γ, 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 (A...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2008-01-01
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| Series: | PPAR Research |
| Online Access: | http://dx.doi.org/10.1155/2008/904041 |
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| author | Giulia Cantini Adriana Lombardi Elisabetta Piscitelli Giada Poli Elisabetta Ceni Sara Marchiani Tonino Ercolino Andrea Galli Mario Serio Massimo Mannelli Michaela Luconi |
| author_facet | Giulia Cantini Adriana Lombardi Elisabetta Piscitelli Giada Poli Elisabetta Ceni Sara Marchiani Tonino Ercolino Andrea Galli Mario Serio Massimo Mannelli Michaela Luconi |
| author_sort | Giulia Cantini |
| collection | DOAJ |
| description | Rosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-γ, 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. |
| format | Article |
| id | doaj-art-e516d14082104ec296040230e5f60ed0 |
| institution | OA Journals |
| issn | 1687-4757 1687-4765 |
| language | English |
| publishDate | 2008-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | PPAR Research |
| spelling | doaj-art-e516d14082104ec296040230e5f60ed02025-08-20T02:21:18ZengWileyPPAR Research1687-47571687-47652008-01-01200810.1155/2008/904041904041Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular SignalingGiulia Cantini0Adriana Lombardi1Elisabetta Piscitelli2Giada Poli3Elisabetta Ceni4Sara Marchiani5Tonino Ercolino6Andrea Galli7Mario Serio8Massimo Mannelli9Michaela Luconi10DENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Gastroenterology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Andrology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Gastroenterology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyDENOthe Center of Excellence for Research, Transfer and High Education: Section of Endocrinology, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini 6, 50139 Firenze, ItalyRosiglitazone (RGZ), a thiazolidinedione ligand of the peroxisome proliferator-activated receptor (PPAR)-γ, 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.http://dx.doi.org/10.1155/2008/904041 |
| spellingShingle | Giulia Cantini Adriana Lombardi Elisabetta Piscitelli Giada Poli Elisabetta Ceni Sara Marchiani Tonino Ercolino Andrea Galli Mario Serio Massimo Mannelli Michaela Luconi Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling PPAR Research |
| title | Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling |
| title_full | Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling |
| title_fullStr | Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling |
| title_full_unstemmed | Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling |
| title_short | Rosiglitazone Inhibits Adrenocortical Cancer Cell Proliferation by Interfering with the IGF-IR Intracellular Signaling |
| title_sort | rosiglitazone inhibits adrenocortical cancer cell proliferation by interfering with the igf ir intracellular signaling |
| url | http://dx.doi.org/10.1155/2008/904041 |
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