| http://purl.uniprot.org/citations/27178332 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/27178332 | http://www.w3.org/2000/01/rdf-schema#comment | "The purpose of this study was to address the role of ESR1 hormone-binding mutations in breast cancer. Soft agar anchorage-independent growth assay, Western blot, ERE reporter transactivation assay, proximity ligation assay (PLA), coimmunoprecipitation assay, silencing assay, digital droplet PCR (ddPCR), Kaplan-Meier analysis, and statistical analysis. It is now generally accepted that estrogen receptor (ESR1) mutations occur frequently in metastatic breast cancers; however, we do not yet know how to best treat these patients. We have modeled the three most frequent hormone-binding ESR1 (HBD-ESR1) mutations (Y537N, Y537S, and D538G) using stable lentiviral transduction in human breast cancer cell lines. Effects on growth were examined in response to hormonal and targeted agents, and mutation-specific changes were studied using microarray and Western blot analysis. We determined that the HBD-ESR1 mutations alter anti-proliferative effects to tamoxifen (Tam), due to cell-intrinsic changes in activation of the insulin-like growth factor receptor (IGF1R) signaling pathway and levels of PIK3R1/PIK3R3. The selective estrogen receptor degrader, fulvestrant, significantly reduced the anchorage-independent growth of ESR1 mutant-expressing cells, while combination treatments with the mTOR inhibitor everolimus, or an inhibitor blocking IGF1R, and the insulin receptor significantly enhanced anti-proliferative responses. Using digital drop (dd) PCR, we identified mutations at high frequencies ranging from 12 % for Y537N, 5 % for Y537S, and 2 % for D538G in archived primary breast tumors from women treated with adjuvant mono-tamoxifen therapy. The HBD-ESR1 mutations were not associated with recurrence-free or overall survival in response in this patient cohort and suggest that knowledge of other cell-intrinsic factors in combination with ESR1 mutation status will be needed determine anti-proliferative responses to Tam."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.org/dc/terms/identifier | "doi:10.1007/s10549-016-3829-5"xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Wang T."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Ando S."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Beyer A.R."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Gu G."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Fuqua S.A.W."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Rechoum Y."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Ludlow A."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Huffman K."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Tsimelzon A."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Gelsomino L."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/author | "Pejerrey S.M."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/date | "2016"xsd:gYear |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/name | "Breast Cancer Res Treat"xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/pages | "253-265"xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/title | "ESR1 mutations affect anti-proliferative responses to tamoxifen through enhanced cross-talk with IGF signaling."xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://purl.uniprot.org/core/volume | "157"xsd:string |
| http://purl.uniprot.org/citations/27178332 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/27178332 |
| http://purl.uniprot.org/citations/27178332 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/27178332 |
| http://purl.uniprot.org/uniprot/#_A0A125SXW0-mappedCitation-27178332 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27178332 |
| http://purl.uniprot.org/uniprot/#_A0A125SXW1-mappedCitation-27178332 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27178332 |
| http://purl.uniprot.org/uniprot/#_Q14268-mappedCitation-27178332 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27178332 |
| http://purl.uniprot.org/uniprot/#_A0A125SXV8-mappedCitation-27178332 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/27178332 |