The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Cyclooxygenase-2 Is Overexpressed in HER-2/neu-positive Breast Cancer
Open accessAbstract
Markedly increased levels of cyclooxygenase-2 (COX-2) mRNA, protein, and prostaglandin E(2) synthesis were detected in HER-2/neu-transformed human mammary epithelial cells (184B5/HER) compared with its nontransformed partner cell line (184B5). HER-2/neu stimulated COX-2 transcription via the Ras --> Raf --> MAPK pathway. The inductive effects of HER-2/neu were mediated, in part, by enhanced binding of AP-1 (c-Jun, c-Fos, and ATF-2) to the cyclic AMP-response element (-59/-53) of the COX-2 promoter. The potential contribution of the transcription factor PEA3 was also investigated. Elevated levels of PEA3 were detected in 184B5/HER cells. A PEA3 site (-75/-72) was identified juxtaposed to the cyclic AMP-response element. HER-2/neu-mediated activation of the COX-2 promoter was blocked by mutagenizing the PEA3 site or overexpressing antisense to PEA3. To determine whether HER-2/neu status was also a determinant of COX-2 expression in vivo, we compared levels of COX-2 protein in HER-2/neu-positive and -negative human breast cancers. Increased amounts of COX-2 were detected in HER-2/neu-positive tumors. Taken together, these results suggest that closely spaced PEA3 and cyclic AMP-response elements are required for HER-2/neu-mediated induction of COX-2 transcription. The clear relationship between HER-2/neu status and COX-2 expression in human breast tumors suggests that this mechanism is likely to be operative in vivo.
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Metadata
- Authors
- Subbaramaiah, K., Norton, L., Gerald, W., & Dannenberg, A. J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-05
- Volume
- 277
- Issue
- 21
- Pages
- 18649-18657
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2041140906
- Cited by
- 317
- References
- 63
- FWCI
- 19.20
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Subbaramaiah, K., Norton, L., Gerald, W., & Dannenberg, A. J. (2002). Cyclooxygenase-2 Is Overexpressed in HER-2/neu-positive Breast Cancer. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m111415200
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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