Expression of AIB1 protein as a prognostic factor in breast cancer

World Journal of Surgical Oncology

Chang Suk Kang²  Byung Joo Song¹  Ahwon Lee²  Kyungji Lee² 

[1] Department of Surgery, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-Gu, Seoul 137-701, Korea;Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, 505 Banpo-dong, Seocho-Gu, Seoul 137-701, Korea

关键词: in situ hybridization;    immunohistochemistry;    AIB1;    neoplasm;    breast;   

Others  :  1206625
DOI  :  10.1186/1477-7819-9-139

 received in 2011-08-04, accepted in 2011-10-29,  发布年份 2011

【 摘 要 】

Background

AIB1 (amplified in breast cancer I) is a member of the p160 steroid receptor coactivator family. AIB1 is frequently overexpressed in breast cancer and has functions that promote oncogenesis that are independent of estrogen receptor (ER) coactivation. We investigated prognostic significance of AIB1 and relationship between AIB1 and ER, progesterone receptor (PR), androgen receptor (AR), DAX-1, and HER2.

Methods

RNA in situ hybridization (ISH) and immunohistochemical (IHC) staining for AIB1, IHC staining for ER and the progesterone receptor (PR) and IHC staining and silver in situ hybridization (SISH) for HER2 were performed for 185 breast cancer cases.

Results

A high level of expression of AIB1 mRNA was observed in 60.0% of tumors. IHC analysis detected AIB1 positivity in 47.3% of tumors, which did not correlate with AIB1 mRNA expression (p = 0.24, r = 0.10). AIB1 protein expression correlated with AR and DAX-1 expression (p = 0.01, r = 0.22 and p = 0.02, r = 0.21, respectively) but not with ER or PR expression (p = 0.14, r = -0.13 and p = 0.16, r = -0.12, respectively). AIB1 protein expression correlated with the amplification of the HER2 gene (p = 0.03, r = 0.19). In contrast to AIB1 protein expression, AIB1 mRNA expression did not correlate with AR, DAX-1, ER, and PR expression, and the amplification of the HER2 gene (p > 0.05 for all).

There were trends that strong AIB1 protein expression correlated with poorer disease free survival (p = 0.07). Strong AIB1 protein expression correlated with poorer overall survival (p = 0.04). Among the ER-negative subgroup, strong AIB1 protein expression correlated with poorer disease free survival and overall survival (p = 0.01 and p < 0.01, respectively).

Conclusions

Strong AIB1 protein expression was poor prognostic factor in breast cancer, especially in ER-negative breast cancers. Further investigation is essential to determine whether AIB1 might be effective therapeutic targets for ER-negative breast cancers.

【 授权许可】

   
2011 Lee et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D: Global cancer statistics. CA: A Cancer Journal for Clinicians 2011, 61:69-90.
• [2]Normanno N, Di Maio M, De Maio E, De Luca A, de Matteis A, Giordano A, Perrone F: Mechanisms of endocrine resistance and novel therapeutic strategies in breast cancer. Endocr Relat Cancer 2005, 12:721-747.
• [3]Robyr D, Wolffe AP, Wahli W: Nuclear hormone receptor coregulators in action: diversity for shared tasks. Molecular endocrinology 2000, 14:329-347.
• [4]Heemers HV, Tindall DJ: Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev 2007, 28:778-808.
• [5]Anzick SL: AIB1, a Steroid Receptor Coactivator Amplified in Breast and Ovarian Cancer. Science 1997, 277:965-968.
• [6]Xu Y, Chen Q, Li W, Su X, Chen T, Liu Y, Zhao Y, Yu C: Overexpression of transcriptional coactivator AIB1 promotes hepatocellular carcinoma progression by enhancing cell proliferation and invasiveness. Oncogene 2010, 29:3386-3397.
• [7]Lahusen T, Henke RT, Kagan BL, Wellstein A, Riegel AT: The role and regulation of the nuclear receptor co-activator AIB1 in breast cancer. Breast Cancer Research and Treatment 2009, 116:225-237.
• [8]Gucalp A, Traina TA: Triple-negative breast cancer: role of the androgen receptor. Cancer J 2010, 16:62-65.
• [9]Zhou XE, Suino-Powell KM, Li J, He Y, Mackeigan JP, Melcher K, Yong EL, Xu HE: Identification of SRC3/AIB1 as a preferred coactivator for hormone-activated androgen receptor. J Biol Chem 2010, 285:9161-9171.
• [10]McShane LM, Altman DG, Sauerbrei W, Taube SE, Gion M, Clark GM: REporting recommendations for tumour MARKer prognostic studies (REMARK). Br J Cancer 2005, 93:387-391.
• [11]Chae BJ, Lee A, Bae JS, Song BJ, Jung SS: Expression of nuclear receptor DAX-1 and androgen receptor in human breast cancer. Journal of surgical oncology 2011, 103:768-772.
• [12]Henke RT, Haddad BR, Kim SE, Rone JD, Mani A, Jessup JM, Wellstein A, Maitra A, Riegel AT: Overexpression of the nuclear receptor coactivator AIB1 (SRC-3) during progression of pancreatic adenocarcinoma. Clin Cancer Res 2004, 10:6134-6142.
• [13]Wolff AC, Hammond ME, Schwartz JN, Hagerty KL, Allred DC, Cote RJ, Dowsett M, Fitzgibbons PL, Hanna WM, Langer A, et al.: American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 2007, 25:118-145.
• [14]Glass CK, Rosenfeld MG: The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev 2000, 14:121-141.
• [15]Brown K, Chen Y, Underhill TM, Mymryk JS, Torchia J: The coactivator p/CIP/SRC-3 facilitates retinoic acid receptor signaling via recruitment of GCN5. J Biol Chem 2003, 278:39402-39412.
• [16]Torchia J, Rose DW, Inostroza J, Kamei Y, Westin S, Glass CK, Rosenfeld MG: The transcriptional co-activator p/CIP binds CBP and mediates nuclear-receptor function. Nature 1997, 387:677-684.
• [17]Torres-Arzayus MI, Font de Mora J, Yuan J, Vazquez F, Bronson R, Rue M, Sellers WR, Brown M: High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene. Cancer Cell 2004, 6:263-274.
• [18]Bouras T, Southey MC, Venter DJ: Overexpression of the steroid receptor coactivator AIB1 in breast cancer correlates with the absence of estrogen and progesterone receptors and positivity for p53 and HER2/neu. Cancer Res 2001, 61:903-907.
• [19]List HJ, Reiter R, Singh B, Wellstein A, Riegel AT: Expression of the nuclear coactivator AIB1 in normal and malignant breast tissue. Breast Cancer Res Treat 2001, 68:21-28.
• [20]Lauritsen KJ, List HJ, Reiter R, Wellstein A, Riegel AT: A role for TGF-beta in estrogen and retinoid mediated regulation of the nuclear receptor coactivator AIB1 in MCF-7 breast cancer cells. Oncogene 2002, 21:7147-7155.
• [21]Hossain A, Kuo MT, Saunders GF: Mir-17-5p regulates breast cancer cell proliferation by inhibiting translation of AIB1 mRNA. Mol Cell Biol 2006, 26:8191-8201.
• [22]Lonard DM, O'Malley BW: SRC-3 transcription-coupled activation, degradation, and the ubiquitin clock: is there enough coactivator to go around in cells? Sci Signal 2008, 1:pe16.
• [23]Zhao C, Yasui K, Lee CJ, Kurioka H, Hosokawa Y, Oka T, Inazawa J: Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis. Cancer 2003, 98:18-23.
• [24]Harigopal M, Heymann J, Ghosh S, Anagnostou V, Camp RL, Rimm DL: Estrogen receptor co-activator (AIB1) protein expression by automated quantitative analysis (AQUA) in a breast cancer tissue microarray and association with patient outcome. Breast Cancer Res Treat 2009, 115:77-85.
• [25]Osborne CK, Bardou V, Hopp TA, Chamness GC, Hilsenbeck SG, Fuqua SA, Wong J, Allred DC, Clark GM, Schiff R: Role of the estrogen receptor coactivator AIB1 (SRC-3) and HER-2/neu in tamoxifen resistance in breast cancer. Journal of the National Cancer Institute 2003, 95:353-361.
• [26]Alkner S, Bendahl PO, Grabau D, Lovgren K, Stal O, Ryden L, Ferno M: AIB1 is a predictive factor for tamoxifen response in premenopausal women. Ann Oncol 2010, 21:238-244.
• [27]Zou JX, Zhong Z, Shi XB, Tepper CG, deVere White RW, Kung HJ, Chen H: ACTR/AIB1/SRC-3 and androgen receptor control prostate cancer cell proliferation and tumor growth through direct control of cell cycle genes. Prostate 2006, 66:1474-1486.
• [28]Zheng FF, Wu RC, Smith CL, O'Malley BW: Rapid estrogen-induced phosphorylation of the SRC-3 coactivator occurs in an extranuclear complex containing estrogen receptor. Mol Cell Biol 2005, 25:8273-8284.
• [29]Conde I, Alfaro JM, Fraile B, Ruiz A, Paniagua R, Arenas MI: DAX-1 expression in human breast cancer: comparison with estrogen receptors ER-alpha, ER-beta and androgen receptor status. Breast Cancer Res 2004, 6:R140-148. BioMed Central Full Text
• [30]Spears M, O S, Migliaccio I, Guiterrez C, Hilsenbeck S, Quintayo MA, Pedraza J, Munro AF, Thomas JS, Kerr GR, Jack WJ, Kunkler IH, Cameron DA, Chetty U, Bartlett JM: The p160 ER co-regulators predict outcome in ER negative breast cancer. Breast Cancer Res Treat 2011.