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NQO1 expression correlates inversely with NFB activation in human breast cancer

Maral Jamshidi, Jirina Bartkova, Dario Greco, Johanna Tommiska, Rainer Fagerholm, Kristiina Aittomäki, Johanna Mattson, Kenneth Villman, Radek Vrtel, Jiri Lukas, Päivi Heikkilä, Carl Blomqvist, Jiri Bartek, Heli Nevanlinna

. 2012 ; 132 (3) : 955-68.

Jazyk angličtina Země Nizozemsko

Perzistentní odkaz   https://www.medvik.cz/link/bmc14073116

Grantová podpora
NS10282 MZ0 CEP - Centrální evidence projektů

Digitální knihovna NLK
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NLK ProQuest Central od 1997-01-01 do Před 1 rokem
Medline Complete (EBSCOhost) od 2005-01-01 do Před 1 rokem
Health & Medicine (ProQuest) od 1997-01-01 do Před 1 rokem
Family Health Database (ProQuest) od 1997-01-01 do Před 1 rokem
Public Health Database (ProQuest) od 1997-01-01 do Před 1 rokem

Odkazy

PubMed 21706157
DOI 10.1007/s10549-011-1629-5
Knihovny.cz E-zdroje

NQO1 participates in cellular defense against oxidative stress and regulates apoptosis via p53- and NFB-mediated pathways. We have previously found that homozygous missense variant NQO1*2 (rs1800566) predicts poor survival among breast cancer patients, particularly after anthracycline-based adjuvant chemotherapy. Here, we investigated NQO1 and NFB protein expression and global gene expression profiles in breast tumors with correlation to tumor characteristics and survival after adjuvant chemotherapy. We used immunohistochemical analysis of tissue microarrays to study NQO1 and NFB expression in two series of tumors: 1000 breast tumors unselected for treatment and 113 from a clinical trial comparing chemotherapy regimens after anthracycline treatment in advanced breast cancer. We used gene expression arrays to define genes co-expressed with NQO1 and NFB. NQO1 and nuclear NFB were expressed in 83% and 11% of breast tumors, and correlated inversely (P = 0.012). NQO1 protein expression was associated with estrogen receptor (ER) expression (P = 0.011), whereas 34.5% of NFB-nuclear/activated tumors were ER negative (P = 0.001). NQO1 protein expression and NFB activation showed only trends, but no statistical significance for patient survival or outcome after anthracycline treatment. Gene expression analysis highlighted 193 genes that significantly correlated with both NQO1 and NFB in opposite directions, consistent with the expression patterns of the two proteins. Inverse correlation was found with genes related to oxidation/reduction, lipid biosynthesis and steroid metabolism, immune response, lymphocyte activation, Jak-STAT signaling and apoptosis. The inverse relationship between NQO1 protein expression and NFB activation, underlined also by inverse patterns of association with ER and gene expression profiles of tumors, suggests that NQO1-NFB interaction in breast cancer is different from several other tissue types, possibly due to estrogen receptor signaling in breast cancer. Neither NQO1 nor NFB protein expression appear as significant prognostic or predictive markers in breast cancer.

Citace poskytuje Crossref.org

Bibliografie atd.

Literatura

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$a NQO1 participates in cellular defense against oxidative stress and regulates apoptosis via p53- and NFB-mediated pathways. We have previously found that homozygous missense variant NQO1*2 (rs1800566) predicts poor survival among breast cancer patients, particularly after anthracycline-based adjuvant chemotherapy. Here, we investigated NQO1 and NFB protein expression and global gene expression profiles in breast tumors with correlation to tumor characteristics and survival after adjuvant chemotherapy. We used immunohistochemical analysis of tissue microarrays to study NQO1 and NFB expression in two series of tumors: 1000 breast tumors unselected for treatment and 113 from a clinical trial comparing chemotherapy regimens after anthracycline treatment in advanced breast cancer. We used gene expression arrays to define genes co-expressed with NQO1 and NFB. NQO1 and nuclear NFB were expressed in 83% and 11% of breast tumors, and correlated inversely (P = 0.012). NQO1 protein expression was associated with estrogen receptor (ER) expression (P = 0.011), whereas 34.5% of NFB-nuclear/activated tumors were ER negative (P = 0.001). NQO1 protein expression and NFB activation showed only trends, but no statistical significance for patient survival or outcome after anthracycline treatment. Gene expression analysis highlighted 193 genes that significantly correlated with both NQO1 and NFB in opposite directions, consistent with the expression patterns of the two proteins. Inverse correlation was found with genes related to oxidation/reduction, lipid biosynthesis and steroid metabolism, immune response, lymphocyte activation, Jak-STAT signaling and apoptosis. The inverse relationship between NQO1 protein expression and NFB activation, underlined also by inverse patterns of association with ER and gene expression profiles of tumors, suggests that NQO1-NFB interaction in breast cancer is different from several other tissue types, possibly due to estrogen receptor signaling in breast cancer. Neither NQO1 nor NFB protein expression appear as significant prognostic or predictive markers in breast cancer.
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