title: An integrative genomic analysis revealed the relevance of microRNA and gene expression for drug-resistance in human breast cancer cells.
abstract: BACKGROUND
  Acquisition of drug-resistance in cancer has led to treatment failure, however, their mechanisms have not been clarified yet. Recent observations indicated that aberrant expressed microRNA (miRNA) caused by chromosomal alterations play a critical role in the initiation and progression of cancer. Here, we performed an integrated genomic analysis combined with array-based comparative hybridization, miRNA, and gene expression microarray to elucidate the mechanism of drug-resistance.
  
  
  RESULTS
  Through genomic approaches in MCF7-ADR; a drug-resistant breast cancer cell line, our results reflect the unique features of drug-resistance, including MDR1 overexpression via genomic amplification and miRNA-mediated TP53INP1 down-regulation. Using a gain of function study with 12 miRNAs whose expressions were down-regulated and genome regions were deleted, we show that miR-505 is a novel tumor suppressive miRNA and inhibits cell proliferation by inducing apoptosis. We also find that Akt3, correlate inversely with miR-505, modulates drug sensitivity in MCF7-ADR.
  
  
  CONCLUSIONS
  These findings indicate that various genes and miRNAs orchestrate to temper the drug-resistance in cancer cells, and thus acquisition of drug-resistance is intricately controlled by genomic status, gene and miRNA expression changes.
authors: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
authors: Yusuke
authors: Y
authors: Yamamoto
authors: Yusuke
authors: Y
authors: Yoshioka
authors: Kaho
authors: K
authors: Minoura
authors: Ryou-u
authors: RU
authors: Takahashi
authors: Fumitaka
authors: F
authors: Takeshita
authors: Toshiki
authors: T
authors: Taya
authors: Reiko
authors: R
authors: Horii
authors: Yayoi
authors: Y
authors: Fukuoka
authors: Takashi
authors: T
authors: Kato
authors: Nobuyoshi
authors: N
authors: Kosaka
authors: Takahiro
authors: T
authors: Ochiya
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D000077143:Docetaxel; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046228:Microarray Analysis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: C574053:MIRN505 microRNA, human; D035683:MicroRNAs; D043823:Taxoids; D000077143:Docetaxel; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt