title: Characterization of β2-microglobulin expression in different types of breast cancer.
abstract: 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.
authors.affiliation: Department of Medicine Biotechnology, Medicine and Science Research Institute of Gansu Province, Lanzhou, China. likesheng63@hotmail.com.
authors.forename: Kesheng
authors.initials: K
authors.lastname: Li
authors.forename: Huifen
authors.initials: H
authors.lastname: Du
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Lian
authors.forename: Suisheng
authors.initials: S
authors.lastname: Yang
authors.forename: Dandan
authors.initials: D
authors.lastname: Chai
authors.forename: Chunya
authors.initials: C
authors.lastname: Wang
authors.forename: Rong
authors.initials: R
authors.lastname: Yang
authors.forename: Xuezhong
authors.initials: X
authors.lastname: Chen
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D005260:Female; D015870:Gene Expression; D020868:Gene Silencing; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D001613:beta 2-Microglobulin / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D001613:beta 2-Microglobulin