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Reports
ErbB-2 Induces Bilateral Adrenal Pheochromocytoma Formation in Mice
Edwin W. Lai, Olga C. Rodriguez, Maral Aventian, Caroline Cromelin, Stanley T. Fricke, Lucia Martiniova, Irina A. Lubensky, Michael P. Lisanti, Kristen L. Picard, James F. Powers, Arthur S. Tischler, Karel Pacak and Chris Albanese
volume 6 | issue 15
1 August 2007Pages: 1946 - 1950
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Pheochromocytoma (PCC) is a rare catecholamine-producing tumor that arises from the adrenal medulla and is often familial. The genetic basis for familial PCC involves mutations of RET, VHL, SHDx or NF-1 in more than 20% of cases. Additional genes may be important in pathogenesis of both familial and sporadic PCC. ErbB-2/Her2/Neu is a growth factor receptor tyrosine kinase that is frequently overexpressed in tumors and there is clinical evidence suggesting that enhanced ErbB-2 growth factor receptor signaling may play a role in PCC. In the present study, ectopic expression of an activated ErbB-2 transgene resulted in bilateral adrenal PCC. Analyses of tumor samples and normal adrenal tissue revealed that levels of the Pten tumor suppressor protein were greatly reduced in PCCs, while levels of the cell cycle regulatory protein cyclin D1 were usually increased. In addition, levels of phospo-AKT were increased in PCCs versus normal adrenal tissue. Biochemical analyses established that PCC’s were functionally active, producing abundant levels of the catecholamines, epinephrine and norepinephrine. These data establish that increased ErbB-2 growth factor receptor signaling in the adrenal medulla can lead to PCC through combined influences on Pten, AKT and cyclin
Authors
Edwin W. Lai
Lombardi Cancer Comprehensive Center; Georgetown University Medical Center; Washington DC and National Institute of Child Health and Human Development; Bethesda, MD USA
Olga C. Rodriguez
Lombardi Cancer Comprehensive Center, Georgetown University Medical Center; Washington DC USA
Maral Aventian
Lombardi Cancer Comprehensive Center, Georgetown University Medical Center; Washington DC USA
Caroline Cromelin
Lombardi Cancer Comprehensive Center, Georgetown University Medical Center; Washington DC USA
Stanley T. Fricke
Lombardi Cancer Comprehensive Center, Georgetown University Medical Center; Washington DC USA
Lucia Martiniova
National Institute of Child Health and Human Development; Bethesda, MD USA
Irina A. Lubensky
National Institute of Neurological Disorders and Stroke; Bethesda, MD USA
Michael P. Lisanti
Thomas Jefferson University; Philadelphia, PA
Kristen L. Picard
Tufts-New England Medical Center; Boston, MA USA
James F. Powers
Tufts-New England Medical Center; Boston, MA USA
Arthur S. Tischler
Tufts-New England Medical Center; Boston, MA USA
Karel Pacak
National Institute of Child Health and Human Development; Bethesda, MD USA
Chris Albanese
Georgetown University Medical Center; Washington DC USA
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.