| http://purl.uniprot.org/citations/19946334 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/19946334 | http://www.w3.org/2000/01/rdf-schema#comment | "Estrogen receptor-alpha (ERalpha) is a major therapeutic target of hormonal therapies in breast cancer, and its expression in tumors is predictive of clinical response. Protein levels of ERalpha are tightly controlled by the 26S proteasome; yet, how the clinical proteasome inhibitor, bortezomib, affects ERalpha regulation has not been studied. Bortezomib selectively inhibits the chymotrypsin-like activity of the proteasome. Unlike other laboratory proteasome inhibitors, bortezomib failed to stabilize ERalpha protein at a dose exceeding 90% inhibition of the chymotrypsin-like activity. Unexpectedly, however, chronic bortezomib exposure caused a reduction of ERalpha levels in multiple ER+ breast cancer cell lines. This response can be explained by the fact that bortezomib induced a dramatic decrease in ERalpha mRNA because of direct transcriptional inhibition and loss of RNA polymerase II recruitment on the ERalpha gene promoter. Bortezomib treatment resulted in promoter-specific changes in estrogen-induced gene transcription that related with occupancy of ERalpha and RNA polymerase II (PolII) on endogenous promoters. In addition, bortezomib inhibited estrogen-dependent growth in soft agar. These results reveal a novel link between proteasome activity and expression of ERalpha in breast cancer and uncover distinct roles of the chymotrypsin-like activity of the proteasome in the regulation of the ERalpha pathway."xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.org/dc/terms/identifier | "doi:10.1038/onc.2009.434"xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/author | "Lee A.V."xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/author | "Alarid E.T."xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/author | "Powers G.L."xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/author | "Ellison-Zelski S.J."xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/author | "Casa A.J."xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/date | "2010"xsd:gYear |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/name | "Oncogene"xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/pages | "1509-1518"xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/title | "Proteasome inhibition represses ERalpha gene expression in ER+ cells: a new link between proteasome activity and estrogen signaling in breast cancer."xsd:string |
| http://purl.uniprot.org/citations/19946334 | http://purl.uniprot.org/core/volume | "29"xsd:string |
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