Chromogranin A Expression in Phaeochromocytomas Associated with von Hippel-Lindau Syndrome and Multiple Endocrine Neoplasia Type 2

S. Cleary; J. K. Phillips; T.-T. Huynh; K. Pacak; S. Fliedner; A. G. Elkahloun; P. Munson; R. A. Worrell; G. Eisenhofer

doi:10.1055/s-2007-993135

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2007; 39(12): 876-883
DOI: 10.1055/s-2007-993135

Original Basic

Chromogranin A Expression in Phaeochromocytomas Associated with von Hippel-Lindau Syndrome and Multiple Endocrine Neoplasia Type 2

S. Cleary¹ ^, ² , J. K. Phillips² , T-T. Huynh¹ , K. Pacak³ , S. Fliedner³ , A. G. Elkahloun⁴ , P. Munson⁵ , R. A. Worrell⁶ , G. Eisenhofer¹

¹Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA
²Division of Health Sciences, Murdoch University and Western Australian Biomedical Research Institute, Perth, WA, Australia
³Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
⁴Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA
⁵Mathematical and Statistical Computing Laboratory, Center for Information Technology, National Institutes of Health, Bethesda, Maryland, USA
⁶Urologic Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Abstract

Chromogranin A (CGA) is a major secretory protein present in the soluble matrix of chromaffin granules of neuroendocrine cells and tumours, such as phaeochromocytomas. CGA has several functions, some of which may be involved in the distinct phenotypic differences of phaeochromocytomas in patients with von Hippel-Lindau (VHL) syndrome compared to multiple endocrine neoplasia type 2 (MEN 2). In this study, we therefore compared tumour and plasma levels of CGA in patients with phaeochromocytoma associated with the two syndromes. We show that phaeochromocytomas from MEN 2 patients express substantially more CGA than tumours from VHL patients at both the mRNA (3-fold greater) and protein (20-fold) level. We further show that relative to increases in plasma catecholamines, patients with phaeochromocytomas associated with MEN 2 have higher plasma concentrations of CGA than those with tumours in VHL syndrome. These data supplement other observations that phaeochromocytomas in VHL compared to MEN 2 patients express lower amounts of catecholamines and other chromaffin granule cargo, such as chromogranin B and neuropeptide Y. Possibly the differences in tumour CGA expression may contribute to differences in secretory vesicle formation and secretion in the two types of tumours. Alternatively the differences in expression in CGA and other secretory constituents may reflect downregulation of the entire regulated secretory pathway in VHL compared to MEN 2 tumours.

Key words

chromaffin cells - catecholamines - noradrenaline - adrenaline - granin - exocytosis

Full Text

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Correspondence

S. Cleary

School of Veterinary and Biomedical Sciences

Murdoch University

6150 Perth WA

Australia

Phone: +61/89/360 66 92

Fax: +61/89/310 41 44

Email: S.Cleary@murdoch.edu.au