ArticleProceedings of the National Academy of Sciences of the United States of America2004
RNA interference of achaete-scute homolog 1 in mouse prostate neuroendocrine cells reveals its gene targets and DNA binding sites.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 48 citations in OpenAlex.
- Neuroendocrine Differentiation of Prostate Cancer-An Intriguing Example of Tumor Evolution at Play.Cancers · 2019Review
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- Mouse Models in Prostate Cancer Translational Research: From Xenograft to PDX.BioMed research international · 2016Review
- SRRM4 Expression and the Loss of REST Activity May Promote the Emergence of the Neuroendocrine Phenotype in Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Article
- Article
- NeuroD1 mediates nicotine-induced migration and invasion via regulation of the nicotinic acetylcholine receptor subunits in a subset of neural and neuroendocrine carcinomas.Molecular biology of the cell · 2014Article
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- FOXO3 shares common targets with ASCL1 genome-wide and inhibits ASCL1-dependent neurogenesis.Cell reports · 2013Article
- A novel function of the proneural factor Ascl1 in progenitor proliferation identified by genome-wide characterization of its targets.Genes & development · 2011Article
- A nutrient-sensitive interaction between Sirt1 and HNF-1α regulates Crp expression.Aging cell · 2011Article
- HES6-1 and HES6-2 function through different mechanisms during neuronal differentiation.PloS one · 2010Article
- LNCaP Atlas: gene expression associated with in vivo progression to castration-recurrent prostate cancer.BMC medical genomics · 2010Article
- Article
- Neural stem cell transcriptional networks highlight genes essential for nervous system development.The EMBO journal · 2009Article
- Combined extrinsic and intrinsic manipulations exert complementary neuronal enrichment in embryonic rat neural precursor cultures: an in vitro and in vivo analysis.The Journal of comparative neurology · 2009Article
- Neuroendocrine differentiation in prostate cancer.American journal of translational research · 2009Article
- NeuroD1 and Mash1 temporally regulate GnRH receptor gene expression in immortalized mouse gonadotrope cells.Molecular and cellular endocrinology · 2008Article
- The proneural basic helix-loop-helix gene ascl1a is required for retina regeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2008Article
- Computational identification and functional validation of regulatory motifs in cartilage-expressed genes.Genome research · 2007Article
- Comparative analysis of regulatory motif discovery tools for transcription factor binding sites.Genomics, proteomics & bioinformatics · 2007Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
We have previously characterized a transgenic mouse model (CR2-TAg) of metastatic prostate cancer arising in the neuroendocrine (NE) cell lineage. Biomarkers of NE differentiation in this model are expressed in conventional adenocarcinoma of the prostate with NE features. To further characterize the pathways that control NE proliferation, differentiation, and survival, we established prostate NE cancer (PNEC) cell lines from CR2-TAg prostate tumors and metastases. GeneChip analyses of cell lines harvested at different passages, and as xenografted tumors, indicated that PNECs express consistent features ex vivo and in vivo and share a remarkable degree of similarity with primary CR2-TAg prostate NE tumors. PNECs express mAsh1, a basic helix-loop-helix (bHLH) transcription factor essential for NE cell differentiation in other tissues. RNA interference knockdown of mAsh1, GeneChip comparisons of treated and control cell populations, and a computational analysis of down-regulated genes identified 12 transcriptional motifs enriched in the gene set. Affected genes, including Adcy9, Hes6, Iapp1, Ndrg4, c-Myb, and Mesdc2, are enriched for a palindromic E-box motif, CAGCTG, indicating that it is a physiologically relevant mAsh1 binding site. The enrichment of a c-Myb binding site and the finding that c-Myb is down-regulated by mAsh1 RNA interference suggest that mAsh1 and c-Myb are in the same signaling pathway. Our data indicate that mAsh1 negatively regulates the cell cycle (e.g., via enhanced Cdkn2d, Bub1 expression), promotes differentiation (e.g., through effects on cAMP), and enhances survival by inhibiting apoptosis. PNEC cell lines should be generally useful for genetic and/or pharmacologic studies of the regulation of NE cell proliferation, differentiation, and tumorigenesis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.