Role of hypoxia and HIF2α in development of the sympathoadrenal cell lineage and chromaffin cell tumors with distinct catecholamine phenotypic features.
Hypoxia has wide-ranging impact in normal physiology and disease processes. This stimulus evokes changes in gene expression mediated by transcription factors termed hypoxia-inducible factors (HIFs) that affect numerous processes: angiogenesis, cell survival, cellular metabolism, stem cell self-renewal and multipotency, migration, invasiveness, and metastatic progression in tumor cells. Over the past decade, increasing numbers of reports have emerged documenting differential roles of HIF1α and HIF2α in these processes. In cells of the sympathoadrenal lineage, both HIFs differentially mediate influences of hypoxia on catecholamine synthesis and secretion, but HIF2α signaling has particularly prominent functions in regulating developmental processes of growth and differentiation. This chapter discusses the role of HIF2α and HIF1α in the context of the development, phenotypic features, and functions of chromaffin cells. Moreover, current knowledge about tumor formation in cells of the sympathoadrenal lineage, leading to catecholamine-producing pheochromocytomas and paragangliomas, is analyzed in the light of the HIF2α signaling network.
Department of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden, Dresden University of Technology, Dresden, Germany. Electronic address: Susan.Richter2@uniklinikum-dresden.de.
Susan
S
Richter
Nan
N
Qin
Karel
K
Pacak
Graeme
G
Eisenhofer
D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism; D019439:Chromaffin Cells / Q000378:metabolism; D005838:Genotype; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D010235:Paraganglioma / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010673:Pheochromocytoma / Q000235:genetics / Q000378:metabolism*
D002395:Catecholamines; D051795:Hypoxia-Inducible Factor 1, alpha Subunit
Catecholamines; Chromaffin cell; Hypoxia; Hypoxia-inducible factor 2; Paraganglioma; Pheochromocytoma; Sympathoadrenal development