FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2094665743> ?p ?o ?g. }

• W2094665743 endingPage "155" @default.
• W2094665743 startingPage "146" @default.
• W2094665743 abstract "ErbB2, a member of the EGF receptor family of tyrosine kinases is overexpressed on many tumor cells of epithelial origin and is the molecular target of trastuzumab (Herceptin), the first humanized antibody used in the therapy of solid tumors. Trastuzumab, which is thought to act, at least in part, by downregulating ErbB2 expression is only effective in ∼30–40% of ErbB2 positive breast tumors. Geldanamycin and its derivative 17-AAG are potential antitumor agents capable of downregulating client proteins of Hsp90, including ErbB2. To investigate the ability of 17-AAG to downregulate ErbB2 in trastuzumab resistant breast cancer cells and the possibility of 17-AAG and trastuzumab potentiating each other's effect, the recently established trastuzumab resistant breast cancer cell line, JIMT-1 was compared to the known trastuzumab sensitive SKBR-3 line. Baseline and stimulus-evoked dimerization and activation levels of ErbB2, and the effects of trastuzumab and 17-AAG alone and in combination on cell proliferation and apoptosis, as well as on ErbB2 expression and phosphorylation have been measured. Baseline activation and amenability to activation and downregulation by trastuzumab was much lower in the resistant line. However, 17-AAG enhanced ErbB2 homodimerization after 5–10 min of treatment in both cell lines, and decreased proliferation with an IC50 of 70 nM for SKBR-3 and 10 nM for JIMT-1. Thus, 17-AAG may be a useful drug in trastuzumab resistant ErbB2 overexpressing tumors. The antiproliferative effect of 17-AAG was positively correlated with phosphorylation and downregulation of ErbB2 and was dominated by apoptosis, although, especially at higher doses, necrosis was also present. Interestingly, IC50 values for ErbB2 downregulation and phosphorylation, in the 30–40 nM range, were not significantly different for the two cell lines. This observation and the negative correlation between resting ErbB2 levels and the antiproliferative effect of 17-AAG may indicate that activation of ErbB2 to some extent could counteract the overall cytostatic effect, especially at higher levels of ErbB2 expression. The usual therapeutic dose of trastuzumab did not change the IC50 of 17-AAG on the proliferation of either cell line, but nevertheless decreased overall ErbB2 phosphorylation and at low doses of 17-AAG further decreased cell growth in the sensitive SKBR-3, thus trastuzumab may be a good combination partner to counteract undesired activating effects of 17-AAG." @default.
• W2094665743 created "2016-06-24" @default.
• W2094665743 creator A5001348816 @default.
• W2094665743 creator A5048298854 @default.
• W2094665743 creator A5056919449 @default.
• W2094665743 creator A5068108014 @default.
• W2094665743 creator A5082945980 @default.
• W2094665743 creator A5085505802 @default.
• W2094665743 date "2006-04-01" @default.
• W2094665743 modified "2023-10-18" @default.
• W2094665743 title "Hsp90 inhibitor 17-AAG reduces ErbB2 levels and inhibits proliferation of the trastuzumab resistant breast tumor cell line JIMT-1" @default.
• W2094665743 cites W156104282 @default.
• W2094665743 cites W1586440254 @default.
• W2094665743 cites W1605766765 @default.
• W2094665743 cites W1627408694 @default.
• W2094665743 cites W1964321121 @default.
• W2094665743 cites W1964826325 @default.
• W2094665743 cites W1972648135 @default.
• W2094665743 cites W1973555911 @default.
• W2094665743 cites W1977059677 @default.
• W2094665743 cites W1982675645 @default.
• W2094665743 cites W1985009080 @default.
• W2094665743 cites W1994485012 @default.
• W2094665743 cites W2001627828 @default.
• W2094665743 cites W2014457594 @default.
• W2094665743 cites W2017397076 @default.
• W2094665743 cites W2020652560 @default.
• W2094665743 cites W2021534705 @default.
• W2094665743 cites W2024651005 @default.
• W2094665743 cites W2025307506 @default.
• W2094665743 cites W2047782251 @default.
• W2094665743 cites W2053503219 @default.
• W2094665743 cites W2098544382 @default.
• W2094665743 cites W2101849511 @default.
• W2094665743 cites W2112417555 @default.
• W2094665743 cites W2116323570 @default.
• W2094665743 cites W2129936304 @default.
• W2094665743 cites W2131851186 @default.
• W2094665743 cites W2135639470 @default.
• W2094665743 cites W2138024261 @default.
• W2094665743 cites W2141346487 @default.
• W2094665743 cites W2141393790 @default.
• W2094665743 cites W2143651667 @default.
• W2094665743 cites W2148860061 @default.
• W2094665743 cites W2150059798 @default.
• W2094665743 cites W2154834163 @default.
• W2094665743 cites W2159203587 @default.
• W2094665743 cites W2162107265 @default.
• W2094665743 cites W2175029576 @default.
• W2094665743 cites W2213952892 @default.
• W2094665743 cites W2222638000 @default.
• W2094665743 cites W2318605753 @default.
• W2094665743 cites W4239989216 @default.
• W2094665743 doi "https://doi.org/10.1016/j.imlet.2005.11.018" @default.
• W2094665743 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16384610" @default.
• W2094665743 hasPublicationYear "2006" @default.
• W2094665743 type Work @default.
• W2094665743 sameAs 2094665743 @default.
• W2094665743 citedByCount "71" @default.
• W2094665743 countsByYear W20946657432012 @default.
• W2094665743 countsByYear W20946657432013 @default.
• W2094665743 countsByYear W20946657432014 @default.
• W2094665743 countsByYear W20946657432015 @default.
• W2094665743 countsByYear W20946657432016 @default.
• W2094665743 countsByYear W20946657432017 @default.
• W2094665743 countsByYear W20946657432018 @default.
• W2094665743 countsByYear W20946657432019 @default.
• W2094665743 countsByYear W20946657432020 @default.
• W2094665743 countsByYear W20946657432021 @default.
• W2094665743 countsByYear W20946657432022 @default.
• W2094665743 crossrefType "journal-article" @default.
• W2094665743 hasAuthorship W2094665743A5001348816 @default.
• W2094665743 hasAuthorship W2094665743A5048298854 @default.
• W2094665743 hasAuthorship W2094665743A5056919449 @default.
• W2094665743 hasAuthorship W2094665743A5068108014 @default.
• W2094665743 hasAuthorship W2094665743A5082945980 @default.
• W2094665743 hasAuthorship W2094665743A5085505802 @default.
• W2094665743 hasConcept C104317684 @default.
• W2094665743 hasConcept C121608353 @default.
• W2094665743 hasConcept C126322002 @default.
• W2094665743 hasConcept C127561419 @default.
• W2094665743 hasConcept C185592680 @default.
• W2094665743 hasConcept C190283241 @default.
• W2094665743 hasConcept C205260736 @default.
• W2094665743 hasConcept C2775932338 @default.
• W2094665743 hasConcept C2779786085 @default.
• W2094665743 hasConcept C2780297055 @default.
• W2094665743 hasConcept C502942594 @default.
• W2094665743 hasConcept C530470458 @default.
• W2094665743 hasConcept C54355233 @default.
• W2094665743 hasConcept C55493867 @default.
• W2094665743 hasConcept C62112901 @default.
• W2094665743 hasConcept C71924100 @default.
• W2094665743 hasConcept C81885089 @default.
• W2094665743 hasConcept C86803240 @default.
• W2094665743 hasConcept C98274493 @default.
• W2094665743 hasConceptScore W2094665743C104317684 @default.
• W2094665743 hasConceptScore W2094665743C121608353 @default.

• next