Arpin downregulation in breast cancer is associated with poor prognosis.

Autor: Lomakina ME; Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Kashirskoe shosse 24, Moscow 115478, Russian Federation., Lallemand F; Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France., Vacher S; Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France., Molinie N; Ecole Polytechnique, CNRS UMR7654, Route de Saclay, 91128 Palaiseau, France., Dang I; Ecole Polytechnique, CNRS UMR7654, Route de Saclay, 91128 Palaiseau, France., Cacheux W; 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., Chipysheva TA; Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Kashirskoe shosse 24, Moscow 115478, Russian Federation., Ermilova VD; Department of Pathology, N.N. Blokhin Cancer Research Center, Moscow 115478, Russia., de Koning L; Department of Translational Research, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005 Paris, France., Dubois T; Department of Translational Research, Institut Curie, PSL Research University, 26 rue d'Ulm, 75005 Paris, France., Bièche I; Pharmacogenomics Unit, Department of Genetics, Institut Curie, 26 rue d'Ulm, 75005 Paris, France., Alexandrova AY; Institute of Carcinogenesis, N.N. Blokhin Cancer Research Center, Kashirskoe shosse 24, Moscow 115478, Russian Federation., Gautreau A; Ecole Polytechnique, CNRS UMR7654, Route de Saclay, 91128 Palaiseau, France.
Jazyk: angličtina
Zdroj: British journal of cancer [Br J Cancer] 2016 Mar 01; Vol. 114 (5), pp. 545-53. Date of Electronic Publication: 2016 Feb 11.
DOI: 10.1038/bjc.2016.18
Abstrakt: 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.
Databáze: MEDLINE
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