Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: UNIPROT:O76050 (
neu
)
3,969
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Overexpression of the oncogene HER2/
neu
(c-erbB-2) occurs in up to 30% of breast cancers and is correlated with reduced survival, especially in node-positive disease. The aim of this study was to identify genes associated with the aggressive phenotype of HER2/
neu
-positive breast cancer cells using cDNA microarrays. RNA was extracted from three HER2/
neu
-positive and three HER2/
neu
-negative breast cancer cell lines. Pooled RNA was hybridized in duplicate to the breast specific microarray filters from Research Genetics containing 5184 unique cDNAs. Subsequently, a similar comparison was performed for pooled RNAs from 10 node-positive, ER-positive invasive ductal carcinomas, half of which were HER2/
neu
overexpressers. In HER2/
neu
overexpressing breast cancer cell lines, 90 (1.7%) genes were up-regulated and 46 (0.9%) were down-regulated, compared to cell lines with low HER2/
neu
protein levels. In contrast, in HER2/
neu
overexpressing primary breast cancers, more genes were down-regulated (N = 132, 2.5%) than up-regulated (N = 19, 0.4%). Many of the differentially expressed genes have previously not been known to play a role in human neoplasia, and some of them may represent novel tumor suppressor or oncogenes. No genes were up-regulated, and only a small number of genes were down-regulated both in cell lines and in carcinomas with high HER2/
neu
protein levels. These included transforming acidic coiled-coil containing protein 1,
glycogen phosphorylase
BB, complement 1q and one EST. The differential expression of select genes was confirmed by Northern blotting (trefoil factor 3) or by immunocytochemistry (
glycogen phosphorylase
BB, vimentin, KAI1). In an extended validation study, 18 of 41 ER-negative, but none of 46 ER-positive, breast carcinomas were found to express vimentin, and all but one of the vimentin-positive tumors were confined to the HER2/
neu
-negative subgroup (P = 0.0019). Our findings support an important role of the mammary stroma in determining the clinical breast cancer phenotype.
...
PMID:Differential gene expression patterns in HER2/neu-positive and -negative breast cancer cell lines and tissues. 1236 91