Expression of activator protein-1 (AP-1) family members in breast cancer.
The 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.



We 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.



We 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).



Expression levels of Fra-1 and Jun-B might be possible biomarkers for prognosis of breast cancer.
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, S-14183, Huddinge, Sweden.|Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.
Amirhossein
A
Razavirad
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, S-14183, Huddinge, Sweden.
Hui
H
Gao
Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran.|Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Reza
R
Ghiasvand
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, S-14183, Huddinge, Sweden.
Chunyan
C
Zhao
Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran. kzendeh@tums.ac.ir.
Kazem
K
Zendehdel
Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, S-14183, Huddinge, Sweden. karin.dahlman-wright@ki.se.
Karin
K
Dahlman-Wright
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D005810:Multigene Family; D016017:Odds Ratio; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics* / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D055815:Young Adult; D000099169:Fos-Related Antigen 1
D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D018808:Transcription Factor AP-1; D000099169:Fos-Related Antigen 1