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Characterization of β2-microglobulin expression in different types of breast cancer.

Li K, Du H, Lian X, Yang S, Chai D, Wang C, Yang R, Chen X - BMC Cancer (2014)

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

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine Biotechnology, Medicine and Science Research Institute of Gansu Province, Lanzhou, China. likesheng63@hotmail.com.

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.

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Related in: MedlinePlus

β2-M IHC staining in breast cancer tissue. A) Strong cytomembrane staining; B) Strong cytoplasm staining; C) Moderate cytoplasm staining; D) Weak cytoplasm staining; E) Negative staining. The tissue sections were examined under a microscope at a magnification of 200×.
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Fig1: β2-M IHC staining in breast cancer tissue. A) Strong cytomembrane staining; B) Strong cytoplasm staining; C) Moderate cytoplasm staining; D) Weak cytoplasm staining; E) Negative staining. The tissue sections were examined under a microscope at a magnification of 200×.

Mentions: The paraffin-embedded sections from the 164 patients’ specimens with breast cancer and the 123 patients with benign breast tumors were immunohistochemically stained using β2-M, ER, PR, HER-2, p53 and Ki67 antibodies (Figure 1). The results demonstrate that 67.68% (111/164) of sections from breast cancer patients were positively stained by the β2-M antibody, which is significantly higher than the 34.14% (42/123) positive staining from patients with benign breast tumors (P < 0.01). No significant correlations were found between β2-M protein expression and age, clinical stage or lymph node metastasis. In addition, 37.03% p53 and 88.40% Ki67 positive staining were found in the breast cancer patient sections, and no significant correlations were found between p53 protein expression and age, clinical stage or lymph node metastasis. The expression of the Ki67 protein had a significant correlation with lymph node metastasis (P < 0.01), but no significant correlation with age or clinical stage (Table 6).Figure 1


Characterization of β2-microglobulin expression in different types of breast cancer.

Li K, Du H, Lian X, Yang S, Chai D, Wang C, Yang R, Chen X - BMC Cancer (2014)

β2-M IHC staining in breast cancer tissue. A) Strong cytomembrane staining; B) Strong cytoplasm staining; C) Moderate cytoplasm staining; D) Weak cytoplasm staining; E) Negative staining. The tissue sections were examined under a microscope at a magnification of 200×.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4197271&req=5

Fig1: β2-M IHC staining in breast cancer tissue. A) Strong cytomembrane staining; B) Strong cytoplasm staining; C) Moderate cytoplasm staining; D) Weak cytoplasm staining; E) Negative staining. The tissue sections were examined under a microscope at a magnification of 200×.
Mentions: The paraffin-embedded sections from the 164 patients’ specimens with breast cancer and the 123 patients with benign breast tumors were immunohistochemically stained using β2-M, ER, PR, HER-2, p53 and Ki67 antibodies (Figure 1). The results demonstrate that 67.68% (111/164) of sections from breast cancer patients were positively stained by the β2-M antibody, which is significantly higher than the 34.14% (42/123) positive staining from patients with benign breast tumors (P < 0.01). No significant correlations were found between β2-M protein expression and age, clinical stage or lymph node metastasis. In addition, 37.03% p53 and 88.40% Ki67 positive staining were found in the breast cancer patient sections, and no significant correlations were found between p53 protein expression and age, clinical stage or lymph node metastasis. The expression of the Ki67 protein had a significant correlation with lymph node metastasis (P < 0.01), but no significant correlation with age or clinical stage (Table 6).Figure 1

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

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine Biotechnology, Medicine and Science Research Institute of Gansu Province, Lanzhou, China. likesheng63@hotmail.com.

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.

Show MeSH
Related in: MedlinePlus