Linked Life Data

7913407

Source:http://linkedlifedata.com/resource/pubmed/id/7913407

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
1994-8-16
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3758-65
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1994
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.
pubmed:affiliation
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't