title: Promoter-level expression clustering identifies time development of transcriptional regulatory cascades initiated by ErbB receptors in breast cancer cells.
abstract: The analysis of CAGE (Cap Analysis of Gene Expression) time-course has been proposed by the FANTOM5 Consortium to extend the understanding of the sequence of events facilitating cell state transition at the level of promoter regulation. To identify the most prominent transcriptional regulations induced by growth factors in human breast cancer, we apply here the Complexity Invariant Dynamic Time Warping motif EnRichment (CIDER) analysis approach to the CAGE time-course datasets of MCF-7 cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). We identify a multi-level cascade of regulations rooted by the Serum Response Factor (SRF) transcription factor, connecting the MAPK-mediated transduction of the HRG stimulus to the negative regulation of the MAPK pathway by the members of the DUSP family phosphatases. The finding confirms the known primary role of FOS and FOSL1, members of AP-1 family, in shaping gene expression in response to HRG induction. Moreover, we identify a new potential regulation of DUSP5 and RARA (known to antagonize the transcriptional regulation induced by the estrogen receptors) by the activity of the AP-1 complex, specific to HRG response. The results indicate that a divergence in AP-1 regulation determines cellular changes of breast cancer cells stimulated by ErbB receptors.
authors.affiliation: Fondazione Bruno Kessler, Via Sommarive 18, I-38123 Povo, Trento, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mina
authors.affiliation: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Magi
authors.affiliation: Fondazione Bruno Kessler, Via Sommarive 18, I-38123 Povo, Trento, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Jurman
authors.affiliation: RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.|RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Itoh
authors.affiliation: RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.|RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Hideya
authors.initials: H
authors.lastname: Kawaji
authors.affiliation: RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.|Telethon Kids Institute, The University of Western Australia, 100 Roberts Road, Subiaco, WA 6008, Australia.
authors.forename: Timo
authors.initials: T
authors.lastname: Lassmann
authors.affiliation: RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.|Department of Medicine at Karolinska Institutet and Center for Metabolism and Endocrinology at Karolinska University Hospital, 141 86, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Arner
authors.affiliation: RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Alistair R R
authors.initials: ARR
authors.lastname: Forrest
authors.affiliation: RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.affiliation: RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Preventive Medicine and Diagnosis Innovation Program (PMI), 2-1 Hirosawa, Wako-shi, Saitama 351-0198, Japan.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Hayashizaki
authors.affiliation: RIKEN Center for Life Science Technologies (Division of Genomic Technologies) (CLST (DGT)), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.|RIKEN Omics Science Center (OSC), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.|Department of Biosciences and Nutrition and Science for Life Laboratory, Karolinska Institutet, Stockholm, SE-141 86, Sweden.
authors.forename: Carsten O
authors.initials: CO
authors.lastname: Daub
authors.affiliation: Laboratory for Integrated Cellular Systems, RIKEN Center for Integrative Medical Sciences (IMS), Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Okada-Hatakeyama
authors.affiliation: Fondazione Bruno Kessler, Via Sommarive 18, I-38123 Povo, Trento, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Furlanello
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D061986:MCF-7 Cells; D011401:Promoter Regions, Genetic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases