期刊论文详细信息
BMC Cancer
Expression of activator protein-1 (AP-1) family members in breast cancer
Amirhossein Kharman-Biz2  Hui Gao1  Reza Ghiasvand3  Chunyan Zhao1  Kazem Zendehdel2  Karin Dahlman-Wright1 
[1] Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, S-14183, Huddinge, Sweden
[2] Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
[3] Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway
关键词: Progesterone receptor;    Estrogen receptor;    Breast cancer;    AP-1 family members;   
Others  :  1079550
DOI  :  10.1186/1471-2407-13-441
 received in 2013-04-05, accepted in 2013-09-25,  发布年份 2013
PDF
【 摘 要 】

Background

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.

Methods

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.

Results

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).

Conclusions

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

【 授权许可】

   
2013 Kharman-Biz et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20141202185013606.pdf 1619KB PDF download
Figure 5. 53KB Image download
Figure 4. 56KB Image download
Figure 3. 54KB Image download
Figure 2. 38KB Image download
Figure 1. 78KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

【 参考文献 】
  • [1]Parkin DM, Bray F, Ferlay J, Pisani P: Global cancer statistics, 2002. CA Canc J Clin 2005, 55:74-108.
  • [2]Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, et al.: Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 2001, 98(19):10869-10874.
  • [3]Sawyers CL: The cancer biomarker problem. Nature 2008, 452(7187):548-552.
  • [4]Potter JD, Cerhan JR, Sellers TA, McGovern PG, Drinkard C, Kushi LR, Folsom AR: Progesterone and estrogen receptors and mammary neoplasia in the Iowa women's health study: how many kinds of breast cancer are there? Canc Epidemiol Biomarkers Prev 1995, 4(4):319-326.
  • [5]Hanna W: Testing for HER2 status. Oncology 2001, 61(Suppl 2):22-30.
  • [6]Weigel MT, Dowsett M: Current and emerging biomarkers in breast cancer: prognosis and prediction. Endocr Relat Canc 2010, 17(4):R245-R262.
  • [7]Ali S, Coombes RC: Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Canc 2002, 2(2):101-112.
  • [8]Pike MC, Spicer DV, Dahmoush L, Press MF: Estrogens, progestogens, normal breast cell proliferation, and breast cancer risk. Epidemiol Rev 1993, 15(1):17-35.
  • [9]Huang W-Y, Newman B, Millikan RC, Schell MJ, Hulka BS, Moorman PG: Hormone-related Factors and Risk of Breast Cancer in Relation to Estrogen Receptor and Progesterone Receptor Status. Am J Epidemiol 2000, 151(7):703-714.
  • [10]Dahlman-Wright K, Cavailles V, Fuqua SA, Jordan VC, Katzenellenbogen JA, Korach KS, Maggi A, Muramatsu M, Parker MG, Gustafsson JA: International Union of Pharmacology. LXIV. Estrogen receptors. Pharmacol Rev 2006, 58(4):773-781.
  • [11]Kushner PJ, Agard DA, Greene GL, Scanlan TS, Shiau AK, Uht RM, Webb P: Estrogen receptor pathways to AP-1. J Steroid Biochem Mol Biol 2000, 74(5):311-317.
  • [12]Milde-Langosch K, Roder H, Andritzky B, Aslan B, Hemminger G, Brinkmann A, Bamberger CM, Loning T, Bamberger AM: The role of the AP-1 transcription factors c-Fos, FosB, Fra-1 and Fra-2 in the invasion process of mammary carcinomas. Breast Canc Res Treat 2004, 86(2):139-152.
  • [13]Angel P, Karin M: The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. Biochim Biophys Acta 1991, 1072(2–3):129-157.
  • [14]Bamberger AM, Methner C, Lisboa BW, Stadtler C, Schulte HM, Loning T, Milde-Langosch K: Expression pattern of the AP-1 family in breast cancer: association of fosB expression with a well-differentiated, receptor-positive tumor phenotype. Int J Canc 1999, 84(5):533-538.
  • [15]Langer S, Singer CF, Hudelist G, Dampier B, Kaserer K, Vinatzer U, Pehamberger H, Zielinski C, Kubista E, Schreibner M: Jun and Fos family protein expression in human breast cancer: correlation of protein expression and clinicopathological parameters. Eur J Gynaecol Oncol 2006, 27(4):345-352.
  • [16]Milde-Langosch K, Janke S, Wagner I, Schroder C, Streichert T, Bamberger AM, Janicke F, Loning T: Role of Fra-2 in breast cancer: influence on tumor cell invasion and motility. Breast Canc Res Treat 2008, 107(3):337-347.
  • [17]Logullo AF, Stiepcich MM, Osorio CA, Nonogaki S, Pasini FS, Rocha RM, Soares FA, Brentani MM: Role of Fos-related antigen 1 in the progression and prognosis of ductal breast carcinoma. Histopathology 2011, 58(4):617-625.
  • [18]Schroder C, Schumacher U, Muller V, Wirtz RM, Streichert T, Richter U, Wicklein D, Milde-Langosch K: The transcription factor Fra-2 promotes mammary tumour progression by changing the adhesive properties of breast cancer cells. Eur J Canc 2010, 46(9):1650-1660.
  • [19]LaValley MP: Logistic regression. Circulation 2008, 117(18):2395-2399.
  • [20]O'Brien KM, Cole SR, Tse CK, Perou CM, Carey LA, Foulkes WD, Dressler LG, Geradts J, Millikan RC: Intrinsic breast tumor subtypes, race, and long-term survival in the carolina breast cancer study. Clin Canc Res 2010, 16(24):6100-6110.
  • [21]El Saghir NS, Seoud M, Khalil MK, Charafeddine M, Salem ZK, Geara FB, Shamseddine AI: Effects of young age at presentation on survival in breast cancer. BMC Canc 2006, 6:194. BioMed Central Full Text
  • [22]Montazeri A, Ebrahimi M, Mehrdad N, Ansari M, Sajadian A: Delayed presentation in breast cancer: a study in Iranian women. BMC Women's Health 2003, 3(1):4. BioMed Central Full Text
  • [23]Mousavi M, Montazeri A, Mohagheghi MA, Mousavi Jarrahi A, Harirchi I, Najafi M, Ebrahimi M: Breast Cancer in Iran: An Epidemiological Review. Breast J 2007, 13(4):383-391.
  • [24]Mousavi SM, Zheng T, Dastgiri S, Miller AB: Age distribution of breast cancer in the middle East, implications for screening. Breast J 2009, 15(6):677-679.
  • [25]Smith LM, Birrer MJ, Stampfer MR, Brown PH: Breast cancer cells have lower activating protein 1 transcription factor activity than normal mammary epithelial cells. Canc Res 1997, 57(14):3046-3054.
  • [26]Chiappetta G, Ferraro A, Botti G, Monaco M, Pasquinelli R, Vuttariello E, Arnaldi L, Di Bonito M, D'Aiuto G, Pierantoni GM, et al.: FRA-1 protein overexpression is a feature of hyperplastic and neoplastic breast disorders. BMC Canc 2007, 7:17. BioMed Central Full Text
  • [27]Belguise K, Milord S, Galtier F, Moquet-Torcy G, Piechaczyk M, Chalbos D: The PKCtheta pathway participates in the aberrant accumulation of Fra-1 protein in invasive ER-negative breast cancer cells. Oncogene 2012, 31(47):4889-4897.
  • [28]Belguise K, Kersual N, Galtier F, Chalbos D: FRA-1 expression level regulates proliferation and invasiveness of breast cancer cells. Oncogene 2005, 24(8):1434-1444.
  • [29]Milde-Langosch K, Kappes H, Riethdorf S, Loning T, Bamberger AM: FosB is highly expressed in normal mammary epithelia, but down-regulated in poorly differentiated breast carcinomas. Breast Canc Res Treat 2003, 77(3):265-275.
  文献评价指标  
  下载次数:49次 浏览次数:17次