期刊论文详细信息
BMC Cancer
Characterization of β2-microglobulin expression in different types of breast cancer
Xuezhong Chen2  Rong Yang1  Chunya Wang3  Dandan Chai3  Suisheng Yang4  Xiaowen Lian3  Huifen Du3  Kesheng Li3 
[1]Department of Surgery, Tumor Hospital of Gansu Province, Lanzhou, China
[2]Department of Pathology, Tumor Hospital of Gansu Province, Lanzhou, China
[3]Department of Medicine Biotechnology, Medicine and Science Research Institute of Gansu Province, Lanzhou, China
[4]Department of Breast Surgery, Tumor Hospital of Gansu Province, Lanzhou, China
关键词: Breast cancer;    Molecular subtypes;    Βeta-2-microglobulin;   
Others  :  1120990
DOI  :  10.1186/1471-2407-14-750
 received in 2014-06-20, accepted in 2014-10-02,  发布年份 2014
PDF
【 摘 要 】

Background

Βeta-2-microglobulin (β2-M) has been demonstrated as a growth factor and signaling molecule in breast cancer and leukemia. The purpose of the study is to characterize β2-M expression in molecular subtypes of breast cancer, thereby investigating the mechanism of β2-M action in breast cancer.

Methods

β2-M and B-Cell Lymphoma/Leukemia 2 (Bcl-2) transcript expression levels in breast cancer tissue and the corresponding normal tissue were quantified using real-time PCR. The protein expression levels of β2-M, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), tumor protein 53 (p53) and Ki67 were determined by immunohistochemical (IHC) staining. Following silencing of the β2-M by siRNA, the levels of Bcl-2, ER, PR and HER-2 transcripts and the protein expression levels in human breast cancer cells were measured by real-time PCR and western blotting, respectively.

Results

The expression of β2-M transcripts demonstrated no significant differences between the four breast cancer molecular subtypes and no significant correlations with age, clinical stage or lymph node metastasis. β2-M transcript expression demonstrated a positive correlation when compared to Bcl-2 transcript expression (P < 0.05). The β2-M protein expression was significantly higher in breast cancer when compared with benign breast tumors (P < 0.01), and have no significant correlation with age, clinical stage or lymph node metastasis. There was a significant difference demonstrated in β2-M protein expression in the four breast cancer molecular subtypes (P < 0.05), and between the ER+ and ER groups (P < 0.01); however, no significant difference was demonstrated between the HER-2+ and HER-2 groups. β2-M protein expression had a negative correlation with ER protein expression (P < 0.01), a positive correlation with p53 protein expression (P < 0.01), and no correlation with Ki67 protein expression. β2-M silencing significantly inhibited Bcl-2 mRNA expression, but did not inhibit ER, PR and HER-2 mRNA expression in MCF-7 cells (ER+, PR+ and HER-2). In addition, Bcl-2 and HER-2 mRNA expression were significantly up-regulated in MDA-MB-231 cells (ER, PR and HER-2), which is consistent with the silencing effect seen at the protein level.

Conclusions

β2-M expression demonstrated a significant difference in the four breast cancer molecular subtypes, and may be related to apoptosis regulation in breast cancer.

【 授权许可】

   
2014 Li et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150211012812442.pdf 816KB PDF download
Figure 2. 63KB Image download
Figure 1. 100KB Image download
【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】
  • [1]Gresswell P, Springer T, Strominger JL, Turner MJ, Grey HM, Kubo RT: Imunological identity of the small subunit of HL-A antigens and β2-microglobulin and its turnover on the cell membrane. Proc Natl Acad Sci 1974, 71:2123-2127.
  • [2]Grey HM, Kubo RT, Colon SM, Poulik MD, Gresswell P, Springer T, Turner MJ, Strominger JM: The small subunit of HL-A antigens is β2-microglobulin. J Exp Med 1973, 138:1608-1612.
  • [3]Karlsson FA, Groth T, Kege K, Wibell L, Peterson PA: Turover in humans of β2-microglobulin. Eur J Clin Invest 1980, 10:293-300.
  • [4]Hansen PB, Olsen NV: Beta 2-microglobulin in medical disease. Ugeskr Laeger 1989, 151:2960-2962.
  • [5]Wibell L: The serum level and urinary excretion of β2 microglobulin in health and renal disease. Pathol Biol 1978, 26:295-301.
  • [6]Klein T, Levin I, Niska A, Koren R, Gal R, Schachter J, Kfir B, Narinski R, Warchaizer S, Klein B: Correlation between tumor and serum β2m expression in patients with breast cancer. Eur J Immunogenet 1996, 23:417-423.
  • [7]Tsimberidou AM, Kantarjian HM, Wen S, O’Brien S, Cortes J, Wierda WG, Koller C, Pierce S, Brandt M, Freireich EJ, Estey EH: The prognostic of serum β2 microglobulin levels in acute myloid leukemia and prognostic scores predicting survival: analysis if 1180 patients. Clin Cancer Res 2008, 14:721-730.
  • [8]Gross M, Top I, Laux I, Katz J, Curran J, Tindell C, Agus D: β-2-microglobulin is an androgen-regulated secreted protein elevated in serum of patients with advanced prostate cancer. Clin Cancer Res 2007, 13:1979-1986.
  • [9]Li KS, Du HF, Lian XW, Yuan M, Liu QJ, Yang SS, Chen XZ, Yang R, Ye WH: Serum β2-microglobulin levels in patients with various solid cancer. J Mol Biomark Diagn 2012, S:2. http://dx.doi.org/10.4172/2155-9929.S2-007 webcite
  • [10]Huang WC, Wu D, Xie Z, Zhao HE, Nomura T, Zayzatoon M, Pohl J, Hsieh CL, Weitzmann MN, Farach-Carson MC, Chung LWK: β2-microglobulin is a signaling and growth-promoting factor for human prostate cancer bone metastasis. Cancer Res 2006, 66:9108-9116.
  • [11]Huang WC, Havel JJ, Zhau HE, Qian WP, Lue HW, Chu CY, Nomura T, Chung LWK: β2-microglobulin signaling blockade inhibited androgen receptor axis and caused apoptosis in human prostate cancer cells. Clin Cancer Res 2008, 14:5341-5347.
  • [12]Huang WC, Zhau HE, Chung LW: Androgen receptor survival signaling is blocked by anti-β2-microblobulin monoclonal antibody via a mitogen-activated protein kinase/lipogenic pathway in human prostate cancer cells. J Biol Chem 2010, 285:7947-7985.
  • [13]Yang J, Qian J, Wezeman M, Wang S, Lin P, Wang M, Yaccoby S, Kwak LW, Barlogie B, Yi Q: Targeting β2-microglobulin for induction of tumor apoptosis in human hematological malignancies. Cancer Cell 2006, 10:295-307.
  • [14]Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, Rees CA, Pollack J, Ross DT, Johnsen H, Aksien LA, Fluge O, Pergamenschikov A, Williams C, Zhu SX, Lonning PE, Borresen-Dale AL, Brown PO, Botstein D: Molecular portraits of human breast tumours. Nature 2000, 406:747-752.
  • [15]Josson S, Nornura T, Lin JT, Huang WC, Wu D, Zhau HE, Zayzafoon M, Weizmann MN, Gururajan M, Chung LW: β2-Microglobulin induces epithelial to mesenchymal transition and confers cancer lethality and bone metastasis in human cancer cells. Cancer Res 2011, 71:2600-2610.
  • [16]Elumatai P, Gunadharini DN, Senthilkunar K, Banudevi S, Arunkumar R, Benson CS, Sharmila G, Arunakaran J: Induction of apoptosis in human breast cancer cells by nimbolide through extrinsic and intrinsic pathway. Toxicol Lett 2012, 215:131-142.
  • [17]Barone I, Brusco L, Fuqua SA: Estrogen receptor mutations and changes in downstream gene expression and signaling. Clin Cancer Res 2010, 16:2702-2708.
  • [18]Yamaguchi Y: Microenvironmental regulation of estrogen signals in breast cancer. Breast Cancer 2007, 14:175-181.
  • [19]Dhar K, Banerjee S, Dhar G, Senqupta K, Banerjee SK: Insulin-like growth factor-1 (IGF-1) induces WISP-2/CCN5 via multiple molecular cross-talks and is essential for mitogenic switch by IGF-1 axis in estrogen receptor-positive breast tumor cells. Cancer Res 2007, 67:1520-1526.
  • [20]Tamimi RM, Colditz GA, Hazra A, Baer HJ, Hankinson SE, Rosner B, Marotti J, Connolly JL, Schnitt SJ, Collins LC: Traditional breast cancer risk factors in relation to molecular subtypes of breast cancer. Breast Cancer Res Treat 2012, 131:159-167.
  • [21]Nomura T, Huang WC, Zhau HE, Wu D, Xie Z, Mimata H, Zayzafoon M, Young AN, Marshall FF, Weitzmann MN, Chung LW: β2-microglobulin promotes the growth of human renal cell carcinoma through the activation of the protein kinase A, cyclic AMP-responsive element-binding protein, and vascular endothelial growth factor axis. Clin Cancer Res 2006, 12:7294-7305.
  • [22]Nomura T, Huang WC, Seo S, Zhau HE, Mimata H, Chung LW: Targeting β2-microglobulin mediated signaling as a novel therapeutic approach or human renal cell carcinoma. J Urol 2007, 178:292-300.
  • [23]Siddiqa A, Long LM, Li L, Marciniak RA, Kazhdan I: Expression of HER-2 in MCF-7 breast cancer cells modulates anti-apoptotic proteins survivin and Bcl-2 via the extracellular signal-related kinase (ERK) and phosphoinositide-3 kinase (PI3K) signalling pathways. BMC Cancer 2008, 8:129. BioMed Central Full Text
  文献评价指标  
  下载次数:1次 浏览次数:6次