title: Arpin downregulation in breast cancer is associated with poor prognosis.
abstract: BACKGROUND
  The Arp2/3 complex is required for cell migration and invasion. The Arp2/3 complex and its activators, such as the WAVE complex, are deregulated in diverse cancers. Here we investigate the expression of Arpin, the Arp2/3 inhibitory protein that antagonises the WAVE complex.
  
  
  METHODS
  We used qRT-PCR and reverse phase protein arrays in a patient cohort with known clinical parameters and outcome, immunofluorescence in breast biopsy cryosections and breast cancer cell lines.
  
  
  RESULTS
  Arpin was downregulated at the mRNA and protein levels in mammary carcinoma cells. Arpin mRNA downregulation was associated with poor metastasis-free survival (MFS) on univariate analysis (P=0.022). High expression of the NCKAP1 gene that encodes a WAVE complex subunit was also associated with poor MFS on univariate analysis (P=0.0037) and was mutually exclusive with Arpin low. Arpin low or NCKAP1 high was an independent prognosis factor on multivariate analysis (P=0.0012) and was strongly associated with poor MFS (P=0.000064).
  
  
  CONCLUSIONS
  Loss of the Arp2/3 inhibitory protein Arpin produces a similar poor outcome in breast cancer as high expression of the NCKAP1 subunit of the Arp2/3 activatory WAVE complex.
authors: Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Kashirskoe shosse 24, Moscow 115478, Russian Federation.
authors: Maria E
authors: ME
authors: Lomakina
authors: Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors: François
authors: F
authors: Lallemand
authors: Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors: Sophie
authors: S
authors: Vacher
authors: Ecole Polytechnique, CNRS UMR7654, Route de Saclay, 91128 Palaiseau, France.
authors: Nicolas
authors: N
authors: Molinie
authors: Ecole Polytechnique, CNRS UMR7654, Route de Saclay, 91128 Palaiseau, France.
authors: Irene
authors: I
authors: Dang
authors: Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.|Department of Medical Oncology, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors: Wulfran
authors: W
authors: Cacheux
authors: Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Kashirskoe shosse 24, Moscow 115478, Russian Federation.
authors: Tamara A
authors: TA
authors: Chipysheva
authors: Department of Pathology, N.N. Blokhin Cancer Research Center, Moscow 115478, Russia.
authors: Valeria D
authors: VD
authors: Ermilova
authors: Department of Translational Research, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005 Paris, France.
authors: Leanne
authors: L
authors: de Koning
authors: Department of Translational Research, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005 Paris, France.
authors: Thierry
authors: T
authors: Dubois
authors: Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France.
authors: Ivan
authors: I
authors: Bièche
authors: Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Kashirskoe shosse 24, Moscow 115478, Russian Federation.
authors: Antonina Y
authors: AY
authors: Alexandrova
authors: Ecole Polytechnique, CNRS UMR7654, Route de Saclay, 91128 Palaiseau, France.
authors: Alexis
authors: A
authors: Gautreau
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism; D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism; D018572:Disease-Free Survival; D015536:Down-Regulation; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D047368:Tumor Burden
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D047628:Estrogen Receptor alpha; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011980:Receptors, Progesterone; C506487:ESR1 protein, human; C484362:NCKAP1 protein, human; C498297:PICk1 protein, human; C000604273:arpin protein, human; C508053:ERBB2 protein, human