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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

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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

Purchase article for $19

Subscribe to this journal for $129/year