Abstract:
:Neuroendocrine (NE) phenotype, seen in >30% of prostate adenocarcinomas (PCa), and NE prostate tumors are implicated in aggressive prostate cancer. Formation of NE prostate tumors in the TRAMP mouse model was suppressed in mice lacking the ubiquitin ligase Siah2, which regulates HIF-1alpha availability. Cooperation between HIF-1alpha and FoxA2, a transcription factor expressed in NE tissue, promotes recruitment of p300 to transactivate select HIF-regulated genes, Hes6, Sox9, and Jmjd1a. These HIF-regulated genes are highly expressed in metastatic PCa and required for hypoxia-mediated NE phenotype, metastasis in PCa, and the formation of NE tumors. Tissue-specific expression of FoxA2 combined with Siah2-dependent HIF-1alpha availability enables a transcriptional program required for NE prostate tumor development and NE phenotype in PCa.
journal_name
Cancer Celljournal_title
Cancer cellauthors
Qi J,Nakayama K,Cardiff RD,Borowsky AD,Kaul K,Williams R,Krajewski S,Mercola D,Carpenter PM,Bowtell D,Ronai ZAdoi
10.1016/j.ccr.2010.05.024subject
Has Abstractpub_date
2010-07-13 00:00:00pages
23-38issue
1eissn
1535-6108issn
1878-3686pii
S1535-6108(10)00236-9journal_volume
18pub_type
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