| http://purl.uniprot.org/citations/23071104 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23071104 | http://www.w3.org/2000/01/rdf-schema#comment | "To understand the mechanisms leading to trastuzumab resistance in HER2-overexpressing breast tumors, we created trastuzumab-insensitive cell lines (SKBR3/100-8 and BT474/100-2). The cell lines maintain HER2 receptor overexpression and show increase in EGF receptor (EGFR). Upon trastuzumab treatment, SKBR3/100-8 and BT474/100-2 cell lines displayed increased growth rate and invasiveness. The trastuzumab resistance in SKBR3/100-8 and BT474/100-2 was accompanied with activation of the Wnt/β-catenin signaling pathway. Further investigation found that Wnt3 overexpression played a key role toward the development of trastuzumab resistance. The expression of Wnt3 in trastuzumab-resistant cells increased nuclear expression of β-catenin and transactivated expression of EGFR. The increased Wnt3 in the trastuzumab-resistant cells also promoted a partial EMT-like transition (epithelial-to-mesenchymal transition); increased N-cadherin, Twist, Slug; and decreased E-cadherin. Knockdown of Wnt3 by siRNA restored cytoplasmic expression of β-catenin and decreased EGFR expression in trastuzumab-resistant cells. Furthermore, the EMT markers were decreased, E-cadherin was increased, and the cell invasiveness was inhibited in response to the Wnt3 downregulation. Conversely, SKBR3 cells which had been stably transfected with full-length Wnt3 exhibited EMT-like transition. The Wnt3 transfectants, SKBR3/Wnt3-7 and SKBR3/Wnt3-9, showed a significant decrease in E-cadherin and increase in N-cadherin, Twist, and Slug. The cells were less sensitive to trastuzumab than parental SKBR3 and vector-transfected cells. In summary, our data suggest that Wnt3 overexpression activates Wnt/β-catenin signaling pathway that leads to transactivation of EGFR and promotes EMT-like transition. This could be an important mechanism leading to trastuzumab resistance in HER2-overexpressing breast cancer cells."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.org/dc/terms/identifier | "doi:10.1158/1541-7786.mcr-12-0155-t"xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/author | "Chung S."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/author | "Kim J."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/author | "Wu Y."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/author | "Ginther C."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/author | "Vadgama J.V."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/author | "Slamon D."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/author | "Mosher N."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/name | "Mol Cancer Res"xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/pages | "1597-1606"xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/title | "Expression of Wnt3 activates Wnt/beta-catenin pathway and promotes EMT-like phenotype in trastuzumab-resistant HER2-overexpressing breast cancer cells."xsd:string |
| http://purl.uniprot.org/citations/23071104 | http://purl.uniprot.org/core/volume | "10"xsd:string |
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