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- W2317481010 abstract "Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FLNKX3.1 is an androgen-regulated, prostate-specific tumor suppressor gene that is essential for development and maintenance of the prostate gland. Loss of Nkx3.1 expression results in the formation of premalignant lesions called prostatic intraepithelial neoplasia lesions (PIN). With additional mutations, these PIN lesions will progress to invasive carcinoma and eventually to metastatic disease in which there is currently no effective treatment. The specific mechanism(s) by which Nkx3.1 suppresses prostate tumorigenesis remains unknown. Previous gene expression profiling studies in Nkx3.1-deficient mouse prostates have shown aberrant expression of many genes that may be involved in prostate tumorigenesis. However, it is unknown whether these genes are direct targets of Nkx3.1 in vivo. To identify direct Nkx3.1 target gens, we used chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-Seq) to identify Nkx3.1 binding sites in the genomes of a human prostate cancer cell line (LNCaP) as well as the normal mouse prostate. We obtained 7 to 15 million uniquely mapped tags each from Nkx3.1 ChIP-seq using LNCaP cells or Nkx3.1+/+, Nkx3.1+/−, and Nkx3.1−/− mouse prostates. This led to the identification of about 8000 Nkx3.1 binding sites in the genome (the Nkx3.1 cistrome). The binding site data were integrated with gene expression profiling results from Nkx3.1 mutant mice to yield a core set of “direct” Nkx3.1 target genes. One gene in particular that is upregulated in Nkx3.1 mutant mice and in human prostate tumors and bound by Nkx3.1 in our ChIP-Seq studies is the receptor activity modifying protein 1 (RAMP1) gene. Ramp1 is a single transmembrane protein that is required for trafficking of the calcitonin gene-related peptide (CGRP) receptor to the plasma membrane. The CGRP receptor binds CGRP, a neuropeptide that has been shown to promote cancer progression. Current studies are focused on whether RAMP1 expression in human prostate cancer cells function to promote tumorigenesis. Given that Ramp1 is localized to the plasma membrane, data from my project may provide support for investigating Ramp1 as a therapeutic target for prostate cancer or for imaging prostate lesions.Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2734. doi:10.1158/1538-7445.AM2011-2734" @default.
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- W2317481010 date "2011-04-15" @default.
- W2317481010 modified "2023-09-27" @default.
- W2317481010 title "Abstract 2734: Genome-wide analysis of direct Nkx3.1 target genes" @default.
- W2317481010 doi "https://doi.org/10.1158/1538-7445.am2011-2734" @default.
- W2317481010 hasPublicationYear "2011" @default.
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