Transcriptomics

Dataset Information

31

Siah2-dependent concerted activity of HIF and FoxA2 regulates formation of neuroendocrine prostate tumors


ABSTRACT: Neuroendocrine (NE) carcinoma and NE differentiation (NED) of human prostate tumor are hallmarks of aggressive human prostate cancer. Here we reveal that HIF-1a cooperation with FoxA2, a transcription factor expressed in NE tissue, is required for determining NE phenotype. Reduced HIF-1a expression, as seen in the E3 ubiquitin ligase Siah2 mutant mice, converted NE tumors to atypical hyperplasia when crossed with the TRAMPTg mice. Significantly, HIF-1a cooperation with FoxA2 enables the trans-activation of select HRE-regulated genes such as Hes6, Plod2 and Jmjd1a, whose expression is notably higher in metastatic prostate adenocarcinomas. Our findings disclose the requirement for spatial and timely regulation of FoxA2 and HIF-1a for NE/NED in prostate tumors. Overall design: 12 prostate tumor samples were analyzed during normoxia and hypoxia, with different FOX/HIF genotypes. The pivotal samples are represented as duplicates.

INSTRUMENT(S): Illumina MouseWG-6 v2.0 expression beadchip

ORGANISM(S): Mus musculus  

SUBMITTER: Roy M Williams  

PROVIDER: GSE18478 | GEO | 2010-07-13

SECONDARY ACCESSION(S): PRJNA120215

REPOSITORIES: GEO

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