title: A class of genes in the HER2 regulon that is poised for transcription in breast cancer cell lines and expressed in human breast tumors.
abstract: HER2-positive breast cancer accounts for 25% of all cases and has a poor prognosis. Although progress has been made in understanding signal transduction, little is known of how HER2 achieves gene regulation. We performed whole genome expression analysis on a HER2⁺ and HER2⁻ breast cancer cell lines and compared these results to expression in 812 primary tumors stratified by their HER2 expression level. Chip-on-chip with anti-RNA polymerase II was compared among breast cancer cell lines to identify genes that are potentially activated by HER2. The expression levels of these HER2-dependent POL II binding genes were determined for the 812 HER2+/- breast cancer tissues. Genes differentially expressed between HER2+/- cell lines were generally regulated in the same direction as in breast cancer tissues. We identified genes that had POLII binding in HER2⁺ cell lines, but without significant gene expression. Of 737 such genes "poised" for expression in cell lines, 113 genes were significantly differentially expressed in breast tumors in a HER2-dependent manner. Pathway analysis of these 113 genes revealed that a large group of genes were associated with stem cell and progenitor cell control as indicated by networks centered on NANOG, SOX2, OCT3/4. HER2 directs POL II binding to a large number of genes in breast cancer cells. A "poised" class of genes in HER2⁺ cell lines with POLII binding and low RNA expression but is differentially expressed in primary tumors, strongly suggests a role of the microenvironment and further suggests a role for stem cells proliferation in HER2-regulated breast cancer tissue.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.
authors.forename: Farah B
authors.initials: FB
authors.lastname: Rahmatpanah
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.|Department of Statistics, University of Akron, Akron, Ohio, USA.|Department of Family and Community Medicine, Northeast Ohio Medical University, Rootstown, Ohio, USA.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Jia
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.
authors.forename: Jessica E
authors.initials: JE
authors.lastname: Char
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.
authors.forename: Bozhao
authors.initials: B
authors.lastname: Men
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.
authors.forename: Anna-Clara
authors.initials: AC
authors.lastname: Franke
authors.affiliation: Department of Cell and Molecular Biology, Tulane University, New Orleans, Louisiana, USA.
authors.forename: Frank E
authors.initials: FE
authors.lastname: Jones
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.|Department of Microbiology and Molecular Genetics, University of California, Irvine, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: McClelland
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Irvine, CA, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Mercola
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D018085:Regulon / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics
chemical_list: D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D012319:RNA Polymerase II; D018719:Erb-b2 Receptor Tyrosine Kinases; D055748:SOXB1 Transcription Factors; C486780:NANOG protein, human; C494173:POU5F1 protein, human; C527782:SOX2 protein, human