Opposing Effects of HIF1M-NM-1 and HIF2M-NM-1 on Chromaffin Cell Phenotypic Features and Tumor Cell Proliferation: Insights from MAX [human]

ABSTRACT: Pheochromocytomas and paragangliomas (PPGLs) are catecholamine-producing tumors with diverse phenotypic features reflecting mutations in numerous genes, including MYC-associated factor X (MAX). To establish whether PPGL phenotypic differences reflect a MAX-mediated mechanism and opposing influences of HIF2M-NM-1 and HIF1M-NM-1, we combined observational investigations in PPGLs and gene-manipulation studies in two pheochromocytoma cell lines. In cell lines lacking Max, re-expression of the gene resulted in maturation of phenotypic features and decreased cell cycle progression. In cell lines lacking Hif2M-NM-1, overexpression of the gene led to immature phenotypic features, failure of dexamethasone to induce differentiation and increased proliferation. HIF1M-NM-1 has opposing actions to HIF2M-NM-1. These model systems explain the features observed in PPGLs due to mutations of MAX and other PPGL susceptibility genes. 88 samples (primary pheochromocytoma (PCC)/paraganglioma tumors) were hybridized onto a cDNA microarray in order to investigate possible heterogeneity within these tumors. This series of tumors is an expansion of GSE19422 that includes nine additional tumors to examine the role of MAX mutations in PCC/PGL.

ORGANISM(S): Homo sapiens

SUBMITTER: Mercedes Robledo 

PROVIDER: E-GEOD-51081 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress