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Accession Number
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ADA566402
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Title
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Tumorigenic Potential of Transit Amplifying Prostate Cells.
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Publication Date
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Jun 2012
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Media Count
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27p
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Personal Author
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S. A. Abdulkadir
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Abstract
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A better understanding of the identities of the target cells responsible for prostate cancer development and the molecular pathways in these cells are essential for the development of new diagnostic, prognostic and therapeutic approaches. We hypothesized that that loss of the prostate tumor suppressor Nkx3.1 sensitizes prostate cancer epithelial cells to further transformation by arresting cells in a precursor transit amplifying state that is more susceptible to tumorigenesis by oncogenes such as c-MYC. Further, we hypothesized that Nkx3.1 function in prostate cells is regulated by the androgen receptor regulator and pioneer factor FoxA1. Our specific goals were to test the susceptibility of Nkx3.1-null transit amplifying cells to transformation and tumorigenicity in response to MYC and to test the hypothesis that FOXA1 is cofactor involved in the regulation of a subset of NKX3.1 target genes in prostate cells. Using transgenic mice and a prostate regeneration tissue recombination system, we obtained evidence that loss of Nkx3.1 cooperates with MYC expression in promoting prostate tumorigenesis in vivo. We have also obtained evidence that Nkx3.1 preferentially binds near FoxA1 binding sites in prostate cells. Nkx3.1 and FoxA1 form a transcriptional complex involved in the regulation of a cohort of target genes with relevance to prostate tumorigenesis.
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Keywords
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Androgens
Arresting gear
Breast cancer
Cells(Biology)
Epithelium
Genes
Hypotheses
Myc oncogene
Neoplasms
Nkx3.1 tumor suppressor
Prostate cancer
Prostate gland
Regeneration(Physiology)
Response(Biology)
Sense organs
Test and evaluation
Transcription(Genetics)
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Source Agency
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Non Paid ADAS
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NTIS Subject Category
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57E - Clinical Medicine
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Corporate Author
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Vanderbilt Univ., Nashville, TN.
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Document Type
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Technical report
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Title Note
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Final rept. 1 Jun 2009-31 May 2012.
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NTIS Issue Number
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1307
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Contract Number
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W81XWH-09-1-0439
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