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BMC Cancer

, 13:441

Translational oncology


BackgroundThe activator protein-1 AP-1 transcription factor is believed to be important in tumorigenesis and altered AP-1 activity was associated with cell transformation. We aimed to assess the potential role of AP-1 family members as novel biomarkers in breast cancer.

MethodsWe studied the expression of AP-1 members at the mRNA level in 72 primary breast tumors and 37 adjacent non-tumor tissues and evaluated its correlation with clinicopathological parameters including estrogen receptor ER, progesterone receptor PR and HER2-neu status. Expression levels of Ubiquitin C UBC were used for normalization. Protein expression of AP-1 members was assessed using Western blot analysis in a subset of tumors. We used student’s t-test, one-way ANOVA, logistic regression and Pearson’s correlation coefficient for statistical analyses.

ResultsWe found significant differences in the expression of AP-1 family members between tumor and adjacent non-tumor tissues for all AP-1 family members except Fos B. Fra-1, Fra-2, Jun-B and Jun-D mRNA levels were significantly higher in tumors compared to adjacent non-tumor tissues p < 0.001, whilst c-Fos and c-Jun mRNA levels were significantly lower in tumors compared with adjacent non-tumor tissues p < 0.001. In addition, Jun-B overexpression had outstanding discrimination ability to differentiate tumor tissues from adjacent non-tumor tissues as determined by ROC curve analysis. Moreover, Fra-1 was significantly overexpressed in the tumors biochemically classified as ERα negative p = 0.012 and PR negative p = 0.037. Interestingly, Fra-1 expression was significantly higher in triple-negative tumors compared with luminal carcinomas p = 0.01.

ConclusionsExpression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer.

KeywordsAP-1 family members Breast cancer Estrogen receptor Progesterone receptor AbbreviationsAP-1Activator protein-1

EREstrogen receptor

PRProgesterone receptor

HER2Human epithermal growth factor receptor 2

UBCUbiquitin C

mRNAMessenger ribonucleic acid

cDNAComplementary deoxyribonucleic acid

Fra-1Fos-related antigen 1

Fra-2Fos-related antigen 2

RT-qPCRReverse transcriptase quantitative polymerase chain reaction

SBR grading systemScarff, Bloom, Richardson, grading system

ROCReceiving operating characteristic

AUCArea under the curve

OROdds ratio

CIConfidence interval

HMECsHuman mammary epithelial cells

ATFActivating transcription factor

MAFMusculoaponeurotic fibrosarcoma.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-13-441 contains supplementary material, which is available to authorized users.

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Autor: Amirhossein Kharman-Biz - Hui Gao - Reza Ghiasvand - Chunyan Zhao - Kazem Zendehdel - Karin Dahlman-Wright


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