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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.
AuthorsMasato Komatsu, Tetsuro Yoshimaru, Taisuke Matsuo, Kazuma Kiyotani, Yasuo Miyoshi, Toshihito Tanahashi, Kazuhito Rokutan, Rui Yamaguchi, Ayumu Saito, Seiya Imoto, Satoru Miyano, Yusuke Nakamura, Mitsunori Sasa, Mitsuo Shimada, Toyomasa Katagiri
JournalInternational journal of oncology (Int J Oncol) Vol. 42 Issue 2 Pg. 478-506 (Feb 2013) ISSN: 1791-2423 [Electronic] Greece
PMID23254957 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Topics
  • Breast Neoplasms (genetics, pathology)
  • Carcinogenesis (genetics)
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic (genetics)
  • Genome, Human
  • Humans
  • Microarray Analysis
  • Transcriptional Activation

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