title: Identification of p130Cas/ErbB2-dependent invasive signatures in transformed mammary epithelial cells.
abstract: Understanding transcriptional changes during cancer progression is of crucial importance to develop new and more efficacious diagnostic and therapeutic approaches. It is well known that ErbB2 is overexpressed in about 25% of human invasive breast cancers. We have previously demonstrated that p130Cas overexpression synergizes with ErbB2 in mammary cell transformation and promotes ErbB2-dependent invasion in three-dimensional (3D) cultures of human mammary epithelial cells. Here, by comparing coding and non-coding gene expression profiles, we define the invasive signatures associated with concomitant p130Cas overexpression and ErbB2 activation in 3D cultures of mammary epithelial cells. Specifically, we have found that genes involved in amino acids synthesis (CBS, PHGDH), cell motility, migration (ITPKA, PRDM1), and angiogenesis (HEY1) are upregulated, while genes involved in inflammatory response (SAA1, S100A7) are downregulated. In parallel, we have shown that the expression of specific miRNAs is altered. Among these, miR-200b, miR-222, miR-221, miR-R210, and miR-424 are upregulated, while miR-27a, miR-27b, and miR-23b are downregulated. Overall, this study presents, for the first time, the gene expression changes underlying the invasive behavior following p130Cas overexpression in an ErbB2 transformed mammary cell model.
authors.affiliation: Molecular Biotechnology Center (MBC); Department of Molecular Biotechnology and Health Sciences; University of Torino; Torino, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Pincini
authors.forename: Giusy
authors.initials: G
authors.lastname: Tornillo
authors.forename: Francesca
authors.initials: F
authors.lastname: Orso
authors.forename: Marianna
authors.initials: M
authors.lastname: Sciortino
authors.forename: Brigitte
authors.initials: B
authors.lastname: Bisaro
authors.forename: Maria Del Pilar Camacho
authors.initials: Mdel P
authors.lastname: Leal
authors.forename: Antonio
authors.initials: A
authors.lastname: Lembo
authors.forename: Maria Felice
authors.initials: MF
authors.lastname: Brizzi
authors.forename: Emilia
authors.initials: E
authors.lastname: Turco
authors.forename: Cristiano
authors.initials: C
authors.lastname: De Pittà
authors.forename: Paolo
authors.initials: P
authors.lastname: Provero
authors.forename: Enzo
authors.initials: E
authors.lastname: Medico
authors.forename: Paola
authors.initials: P
authors.lastname: Defilippi
authors.forename: Daniela
authors.initials: D
authors.lastname: Taverna
authors.forename: Sara
authors.initials: S
authors.lastname: Cabodi
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology; D002461:Cell Line, Transformed; D002465:Cell Movement; D050719:Crk-Associated Substrate Protein / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism* / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D042361:Mammary Glands, Human / Q000473:pathology*; D051150:Methionine Sulfoxide Reductases / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D050543:Phosphoglycerate Dehydrogenase / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: D050719:Crk-Associated Substrate Protein; D051150:Methionine Sulfoxide Reductases; D035683:MicroRNAs; D008840:Microfilament Proteins; D050543:Phosphoglycerate Dehydrogenase; D018719:Erb-b2 Receptor Tyrosine Kinases; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D014157:Transcription Factors; C089242:S100A7 protein, human; C120376:MSRB2 protein, human; C508053:ERBB2 protein, human
keywords: ErbB2; breast cancer; gene expression; invasion; miRNA; p130Cas