title: Molecular features of triple negative breast cancer cells by genome-wide             gene expression profiling analysis.
abstract: Triple negative breast cancer (TNBC) has a poor outcome due to the lack of beneficial therapeutic targets. To clarify the molecular mechanisms involved in the carcinogenesis of TNBC and to identify target molecules for novel anticancer drugs, we analyzed the gene expression profiles of 30 TNBCs as well as 13 normal epithelial ductal cells that were purified by laser-microbeam microdissection. We identified 301 and 321 transcripts that were significantly upregulated and downregulated in TNBC, respectively. In particular, gene expression profile analyses of normal human vital organs allowed us to identify 104 cancer-specific genes, including those involved in breast carcinogenesis such as NEK2, PBK and MELK. Moreover, gene annotation enrichment analysis revealed prominent gene subsets involved in the cell cycle, especially mitosis. Therefore, we focused on cell cycle regulators, asp (abnormal spindle) homolog, microcephaly-associated (Drosophila) (ASPM) and centromere protein K (CENPK) as novel therapeutic targets for TNBC. Small-interfering RNA-mediated knockdown of their expression significantly attenuated TNBC cell viability due to G1 and G2/M cell cycle arrest. Our data will provide a better understanding of the carcinogenesis of TNBC and could contribute to the development of molecular targets as a treatment for TNBC patients.
authors.affiliation: Division of Genome Medicine, Institute for Genome Research, The                     University of Tokushima, Tokushima, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Komatsu
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Yoshimaru
authors.forename: Taisuke
authors.initials: T
authors.lastname: Matsuo
authors.forename: Kazuma
authors.initials: K
authors.lastname: Kiyotani
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Miyoshi
authors.forename: Toshihito
authors.initials: T
authors.lastname: Tanahashi
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Rokutan
authors.forename: Rui
authors.initials: R
authors.lastname: Yamaguchi
authors.forename: Ayumu
authors.initials: A
authors.lastname: Saito
authors.forename: Seiya
authors.initials: S
authors.lastname: Imoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Miyano
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sasa
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Toyomasa
authors.initials: T
authors.lastname: Katagiri
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D063646:Carcinogenesis / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D046228:Microarray Analysis; D015533:Transcriptional Activation