| http://purl.uniprot.org/citations/31536510 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/31536510 | http://www.w3.org/2000/01/rdf-schema#comment | "In treating patients with castration resistant prostate cancer (CRPC), enzalutamide, the second-generation androgen receptor (AR) antagonist, is an accepted standard of care. However, clinical benefits are limited to a median time of 4.8 months because resistance inevitably emerges. To determine the mechanism of treatment resistance, we carried out a RNA sequence analysis and found increased expression levels of neuroendocrine markers in the enzalutamide-resistant LNCaP human prostate cancer (CaP) cell line when compared to the parental cell line. Subsequent studies demonstrated that Transcription Factor-4 (TCF4), a transcription factor implicated in WNT signaling, mediated neuroendocrine differentiation (NED) in response to enzalutamide treatment and was elevated in the enzalutamide-resistant LNCaP. In addition, we observed that PTHrP mediated enzalutamide resistance in tissue culture and inducible TCF4 overexpression resulted in enzalutamide-resistance in a mouse xenograft model. Finally, small molecule inhibitors of TCF4 or PTHrP partially reversed enzalutamide resistance in CaP cells. When tissues obtained from men who died of metastatic CaP were examined, a positive correlation was found between the expression levels of TCF4 and PTHrP. Taken together, the current results indicate that TCF4 induces enzalutamide resistance via NED in CaP."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.org/dc/terms/identifier | "doi:10.1371/journal.pone.0213488"xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/author | "Kim W.T."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/author | "Kim W.J."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/author | "Rosenfeld J.A."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/author | "Kwon Y.S."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/author | "Kim I.Y."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/author | "Mehra R."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/author | "Palapattu G."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/author | "Lee G.T."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/date | "2019"xsd:gYear |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/name | "PLoS One"xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/pages | "e0213488"xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/title | "TCF4 induces enzalutamide resistance via neuroendocrine differentiation in prostate cancer."xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://purl.uniprot.org/core/volume | "14"xsd:string |
| http://purl.uniprot.org/citations/31536510 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/31536510 |
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