| pubmed-article:7913407 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C0678222 | lld:lifeskim |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C1518174 | lld:lifeskim |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C0596402 | lld:lifeskim |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C0206364 | lld:lifeskim |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C0012899 | lld:lifeskim |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C0004083 | lld:lifeskim |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:7913407 | lifeskim:mentions | umls-concept:C2349975 | lld:lifeskim |
| pubmed-article:7913407 | pubmed:issue | 14 | lld:pubmed |
| pubmed-article:7913407 | pubmed:dateCreated | 1994-8-16 | lld:pubmed |
| pubmed-article:7913407 | pubmed:abstractText | The c-erbB-2 (HER-2/neu) protooncogene encodes an M(r) 185,000 transmembrane glycoprotein with intrinsic tyrosine kinase activity. Agonistic antibodies against p185c-erbB-2 enhance the cytotoxic effect of the DNA alkylator, cisplatin, against c-erbB-2-overexpressing human carcinoma cells (Hancock et al., Cancer Res., 51:4575-4580, 1991). We have studied the possible association between receptor signal transduction and cisplatin-mediated cytotoxicity utilizing the SKBR-3 human breast cancer cell line and the anti-p185 TAb 250 IgG1. TAb 250 induced tyrosine phosphorylation of p185 and the receptor substrate phospholipase C-gamma 1, as well as rapid association of these molecules in vivo. Simultaneously with phosphorylation, phospholipase C-gamma 1 catalytic activity measured in a [3H]phosphatidylinositol-4,5-bisphosphate hydrolysis assay was increased 61 +/- 12% above control. Preincubation of SKBR-3 cells with the tyrosine kinase inhibitor tyrphostin 50864-2 abrogated the enhancement of drug-mediated cell kill induced by TAb 250. The supraadditive drug/antibody effect was not seen in SKBR-3 cells with TAb 263, an anti-p185 IgG1 that does not induce receptor signaling or with TAb 250 in MDA-468 breast cancer cells which do not overexpress c-erbB-2. In addition, transforming growth factor-alpha increased cisplatin-induced cytotoxicity against NIH 3T3 cells overexpressing an epidermal growth factor receptor/c-erbB-2 chimera. Cellular uptake or efflux of [195mPt]cisplatin by SKBR-3 cells was not altered by TAb 250. Finally, simultaneous treatment of SKBR-3 cells with TAb 250 and cisplatin increased cisplatin/DNA intrastrand adduct formation and delayed the rate of adduct decay. Taken together these data support a direct association between p185c-erbB-2 signal transduction and inhibition of cisplatin-induced DNA repair. | lld:pubmed |
| pubmed-article:7913407 | pubmed:language | eng | lld:pubmed |
| pubmed-article:7913407 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:7913407 | pubmed:citationSubset | IM | lld:pubmed |
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| pubmed-article:7913407 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:7913407 | pubmed:month | Jul | lld:pubmed |
| pubmed-article:7913407 | pubmed:issn | 0008-5472 | lld:pubmed |
| pubmed-article:7913407 | pubmed:author | pubmed-author:PoirierM CMC | lld:pubmed |
| pubmed-article:7913407 | pubmed:author | pubmed-author:StewartS JSJ | lld:pubmed |
| pubmed-article:7913407 | pubmed:author | pubmed-author:ArteagaC LCL | lld:pubmed |
| pubmed-article:7913407 | pubmed:author | pubmed-author:ShawverL KLK | lld:pubmed |
| pubmed-article:7913407 | pubmed:author | pubmed-author:HurdS DSD | lld:pubmed |
| pubmed-article:7913407 | pubmed:author | pubmed-author:WinnierA RAR | lld:pubmed |
| pubmed-article:7913407 | pubmed:author | pubmed-author:Lopez-Larraza... | lld:pubmed |
| pubmed-article:7913407 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:7913407 | pubmed:day | 15 | lld:pubmed |
| pubmed-article:7913407 | pubmed:volume | 54 | lld:pubmed |
| pubmed-article:7913407 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:7913407 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:7913407 | pubmed:pagination | 3758-65 | lld:pubmed |
| pubmed-article:7913407 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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| pubmed-article:7913407 | pubmed:meshHeading | pubmed-meshheading:7913407-... | lld:pubmed |
| pubmed-article:7913407 | pubmed:year | 1994 | lld:pubmed |
| pubmed-article:7913407 | pubmed:articleTitle | p185c-erbB-2 signal enhances cisplatin-induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair. | lld:pubmed |
| pubmed-article:7913407 | pubmed:affiliation | Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee. | lld:pubmed |
| pubmed-article:7913407 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:7913407 | pubmed:publicationType | Research Support, U.S. Gov't, Non-P.H.S. | lld:pubmed |
| pubmed-article:7913407 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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