cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells

To investigate changes in gene expression associated with ERBB2 , expression profiling of immortalized human mammary luminal epithelial cells and variants expressing a moderate and high level of ERBB2 has been carried out using cDNA microarrays corresponding to approximately 6000 unique genes/ESTs....

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Veröffentlicht in:Oncogene 2003-05, Vol.22 (17), p.2680-2688
Hauptverfasser: Mackay, Alan, Jones, Chris, Dexter, Tim, Silva, Ricardo L A, Bulmer, Karen, Jones, Allison, Simpson, Peter, Harris, Robert A, Jat, Parmjit S, Neville, A Munro, Reis, Luiz F L, Lakhani, Sunil R, O'Hare, Michael J
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container_end_page 2688
container_issue 17
container_start_page 2680
container_title Oncogene
container_volume 22
creator Mackay, Alan
Jones, Chris
Dexter, Tim
Silva, Ricardo L A
Bulmer, Karen
Jones, Allison
Simpson, Peter
Harris, Robert A
Jat, Parmjit S
Neville, A Munro
Reis, Luiz F L
Lakhani, Sunil R
O'Hare, Michael J
description To investigate changes in gene expression associated with ERBB2 , expression profiling of immortalized human mammary luminal epithelial cells and variants expressing a moderate and high level of ERBB2 has been carried out using cDNA microarrays corresponding to approximately 6000 unique genes/ESTs. A total of 61 significantly up- or downregulated (2.0-fold) genes were identified and further validated by RT–PCR analysis as well as microarray comparisons with a spontaneously ERBB2 - overexpressing breast cancer cell line and ERBB2 -positive primary breast tumors. The expression and clinical relevance of proteins predicted to be associated with ERBB2 overexpression in breast cancers were analysed together with their clinical relevance by antibody screening using a tissue array. Differentially regulated genes include those involved in cell–matrix interactions including proline 4-hydroxylase ( P4HA2 ), galectin 1 ( LGALS1 ) and galectin 3 ( LGALS3 ), fibronectin 1 ( FN1 ) and p-cadherin ( CDH3 ), and cell proliferation ( CRIP1 , IGFBP3 ) and transformation ( S100P , S100A4 ). A number of genes associated with MYC signalling were also differentially expressed, including NDRG1 , USF2 and the epithelial membrane proteins 1 and 3 ( EMP1 , EMP3 ). These data represent profiles of the transcriptional changes associated with ERBB2 -related pathways in the breast, and identify novel and potentially useful targets for prognosis and therapy.
doi_str_mv 10.1038/sj.onc.1206349
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subjects Apoptosis
Biological and medical sciences
Breast - metabolism
Breast cancer
Breast Neoplasms - metabolism
Cadherins
Carcinoma - metabolism
Cell Biology
Cell proliferation
Classical genetics, quantitative genetics, hybrids
DNA microarrays
Epithelial cells
Epithelium - metabolism
ErbB-2 protein
Female
Fibronectin
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Profiling
Genetics of eukaryotes. Biological and molecular evolution
Human
Human Genetics
Humans
Hydroxylase
In Vitro Techniques
Insulin-like growth factor-binding protein 3
Internal Medicine
Mammary gland
Medicine
Medicine & Public Health
Membrane proteins
Myc protein
Oligonucleotide Array Sequence Analysis
oncogenomics
Oncology
Proline
Receptor, ErbB-2 - biosynthesis
Receptor, ErbB-2 - genetics
Reverse Transcriptase Polymerase Chain Reaction
S100A4 protein
Signal transduction
Transcription
Tumor Cells, Cultured
Tumors
title cDNA microarray analysis of genes associated with ERBB2 (HER2/neu) overexpression in human mammary luminal epithelial cells
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