Document Detail


High expression of ATP-binding cassette transporter ABCC11 in breast tumors is associated with aggressive subtypes and low disease-free survival.
MedLine Citation:
PMID:  23288347     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
ATP-binding cassette (ABC) transporters are membrane proteins that efflux various compounds from cells, including chemotherapeutic agents, and are known to affect multidrug resistance. Recent reports disagree on whether ABCC11 is a risk factor for breast tumorigenesis, but its expression in breast cancer is poorly investigated. We hypothesized that both frequency and expression levels of ABC transporters in breast tumors would vary by cancer subtype, and be associated with prognosis. Here, we constructed a tissue microarray breast tumor samples from 281 patients, and analyzed expressions of ABCB1, ABCC1, ABCC11, and ABCG2 immunohistochemically. Breast cancer subtypes were determined by immunohistochemistry of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Protein expression was correlated to clinicopathological characteristics, clinical follow-up, and pathological complete response to neoadjuvant chemotherapy. The tissue microarray comprised 191 luminal A (68.0 %), 17 luminal B (6.0 %), 27 HER2 (9.6 %), and 46 triple-negative (16.4 %) samples. ABCC1 and ABCC11 expressions were associated with significantly shorter disease-free survival (P = 0.027 and P = 0.003, respectively). ABCC1, ABCC11, and ABCG2, but not ABCB1, were expressed significantly more, and more frequently, in aggressive subtypes. Patients with HER2+ and triple-negative tumor subtypes that expressed high levels of ABCC11 had significantly worse disease-free survival (P = 0.017 and P < 0.001, respectively). We have shown, for the first time, that ABCC1, ABCC11, and ABCG2 are highly expressed in aggressive breast cancer subtypes, and that tumor ABCC11 expression is associated with poor prognosis.
Authors:
Akimitsu Yamada; Takashi Ishikawa; Ikuko Ota; Mariko Kimura; Daisuke Shimizu; Mikiko Tanabe; Takashi Chishima; Takeshi Sasaki; Yasushi Ichikawa; Satoshi Morita; Koh-ichiro Yoshiura; Kazuaki Takabe; Itaru Endo
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-01-04
Journal Detail:
Title:  Breast cancer research and treatment     Volume:  137     ISSN:  1573-7217     ISO Abbreviation:  Breast Cancer Res. Treat.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-06-27     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  8111104     Medline TA:  Breast Cancer Res Treat     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  773-82     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics,  metabolism*
Aged
Aged, 80 and over
Breast Neoplasms / drug therapy,  metabolism*,  mortality*,  pathology
Disease Progression
Female
Gene Expression
Genotype
Humans
Middle Aged
Multidrug Resistance-Associated Proteins / genetics,  metabolism
Neoadjuvant Therapy
Neoplasm Staging
Prognosis
Grant Support
ID/Acronym/Agency:
K12HD055881/HD/NICHD NIH HHS; P30 CA016059/CA/NCI NIH HHS; R01 CA160688/CA/NCI NIH HHS; R01CA160688/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/ABCC11 protein, human; 0/Multidrug Resistance-Associated Proteins; 0/multidrug resistance-associated protein 1
Comments/Corrections
Comment In:
Breast Cancer Res Treat. 2013 Apr;138(2):651   [PMID:  23443291 ]
Breast Cancer Res Treat. 2013 Apr;138(2):652-3   [PMID:  23646373 ]

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