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http://purl.uniprot.org/citations/15958618http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15958618http://www.w3.org/2000/01/rdf-schema#comment"

Purpose

In a previous gene expression array study, we identified some 300 genes that were differentially expressed in human epidermal growth factor receptor tyrosine kinase 2 (HER2)-positive versus HER2-negative breast cancer cells. We have now done validation experiments on a group of three cell membrane components that had previously not been implicated in breast cancer. We also studied the expression of three other cell membrane proteins known to play a role in mammary neoplasia.

Experimental design

By immunohistochemistry, we examined up to 130 archival breast carcinomas for Celsr2, E-cadherin, Kai1, and CD9 expression. The expression levels of NET-6 and TROP-2 were determined by quantitative reverse transcription-PCR in a subset of frozen tumors. We also studied fresh pellets and paraffin-embedded cell buttons of nine human breast cell lines. The relationship between the expression of all six membrane proteins and a variety of pathologic and biological variables, including estrogen receptor, HER2, and epidermal growth factor receptor status, was also examined. The NET-6 gene was transfected into a low-expressing cell line, and the effect on cellular morphology, growth, and invasion in vitro was recorded.

Results

Celsr2 was down-regulated in one cell line and in 7% of breast cancers. E-cadherin, Kai1, and CD9 were down-regulated in 35%, 76%, and 79% of tumors, respectively, confirming the important role of these markers in human mammary neoplasia. In breast cancer cell lines and tissues, TROP-2 was generally expressed at low levels, although a few specimens showed relative overexpression. NET-6 levels were lower in HER2-negative breast carcinoma cells. In addition, NET-6 was markedly down-regulated in estrogen receptor-negative breast cancers, and expression was lowest in "basal-like" tumors. Ectopic expression of NET-6 in low-expressing MDA-MB-231 cells altered cellular morphology, inhibited growth in vitro, and decreased invasion in a Boyden chamber assay.

Conclusions

We have confirmed the expression of three new membrane markers that had previously not been implicated in human breast cancer, and one of them (NET-6) was correlated with HER2 and estrogen receptor status. NET-6 levels were decreased in estrogen receptor-negative and high-grade tumors, and ectopic expression of this gene had an inhibitory effect on proliferation and invasion. Thus, NET-6 may represent a novel breast cancer suppressor gene."xsd:string
http://purl.uniprot.org/citations/15958618http://purl.org/dc/terms/identifier"doi:10.1158/1078-0432.ccr-04-2107"xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/author"Huang H."xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/author"Sossey-Alaoui K."xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/author"Hawthorn L."xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/author"Geradts J."xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/author"Groth J."xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/author"Beall S."xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/date"2005"xsd:gYear
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/name"Clin Cancer Res"xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/pages"4357-4364"xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/title"Aberrant expression of novel and previously described cell membrane markers in human breast cancer cell lines and tumors."xsd:string
http://purl.uniprot.org/citations/15958618http://purl.uniprot.org/core/volume"11"xsd:string
http://purl.uniprot.org/citations/15958618http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15958618
http://purl.uniprot.org/citations/15958618http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15958618
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http://purl.uniprot.org/uniprot/#_O95857-mappedCitation-15958618http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15958618
http://purl.uniprot.org/uniprot/#_Q6FGK0-mappedCitation-15958618http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15958618
http://purl.uniprot.org/uniprot/O95857http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/15958618
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