| http://purl.uniprot.org/citations/22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22739988 | http://www.w3.org/2000/01/rdf-schema#comment | "The insulin-like growth factor-1 receptor (IGF-1R) signaling pathway is critical for both normal mammary gland development and malignant transformation. It has been reported that the IGF-1 stimulates breast cancer cell proliferation and is upregulated in tumors with BRCA1/2 mutations. We report here that IGF-1 is negatively regulated by BRCA1 at the transcriptional level in human breast cancer cells. BRCA1 knockdown (BRCA1-KD) induces the expression of IGF-1 mRNA in MCF7 cells in an estrogen receptor α (ERα)-dependent manner. We found that both BRCA1 and ERα bind to the endogenous IGF-1 promoter region containing an estrogen-responsive element-like (EREL) site. BRCA1-KD does not significantly affect ERα binding on the IGF-1 promoter. Reporter analysis demonstrates that BRCA1 could regulate IGF-1 transcripts via this EREL site. In addition, enzyme-linked immunosorbent assay revealed that de-repression of IGF-1 transcription by BRCA1-KD increases the level of extracellular IGF-1 protein, and secreted IGF-1 seems to increase the phospho-IGF-1Rβ and activate its downstream signaling pathway. Blocking the IGF-1/IGF-1R/phosphoinositide 3-kinase (PI3K)/AKT pathway either by a neutralizing antibody or by small-molecule inhibitors preferentially reduces the proliferation of BRCA1-KD cells. Furthermore, the IGF-1-EREL-Luc reporter assay demonstrates that various inhibitors, which can inhibit the IGF-1R pathway, can suppress this reporter activity. These findings suggest that BRCA1 defectiveness keeps turning on IGF-1/PI3K/AKT signaling, which significantly contributes to increase cell survival and proliferation."xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.org/dc/terms/identifier | "doi:10.1038/cddis.2012.78"xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/author | "Kim H.J."xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/author | "Kang H.J."xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/author | "Seong Y.S."xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/author | "Hong Y.B."xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/author | "Bae I."xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/author | "Yi Y.W."xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/name | "Cell Death Dis"xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/pages | "e336"xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/title | "BRCA1 negatively regulates IGF-1 expression through an estrogen-responsive element-like site."xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://purl.uniprot.org/core/volume | "3"xsd:string |
| http://purl.uniprot.org/citations/22739988 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22739988 |
| http://purl.uniprot.org/citations/22739988 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/22739988 |
| http://purl.uniprot.org/uniprot/#_A0A1U9WZ84-mappedCitation-22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22739988 |
| http://purl.uniprot.org/uniprot/#_Q13429-mappedCitation-22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22739988 |
| http://purl.uniprot.org/uniprot/#_P05019-mappedCitation-22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22739988 |
| http://purl.uniprot.org/uniprot/#_P31749-mappedCitation-22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22739988 |
| http://purl.uniprot.org/uniprot/#_Q5U743-mappedCitation-22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22739988 |
| http://purl.uniprot.org/uniprot/#_Q6LD41-mappedCitation-22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22739988 |
| http://purl.uniprot.org/uniprot/#_Q59GC5-mappedCitation-22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22739988 |
| http://purl.uniprot.org/uniprot/#_Q9NP10-mappedCitation-22739988 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/22739988 |
| http://purl.uniprot.org/uniprot/Q9NP10 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/22739988 |