The Effect Of MICA Expression On The Pathogenesis And Anti-tumor Effect Of Breast Cancer

Objective: To investigate the association of MICA alleles polymorphisms with breast cancer; study the expression of membrane MICA(mMICA) and secretory MICA(sMICA) in different malignant degree of breast cancers; Study the effect of expression regulating of MICA on cytotoxicity of NK cells to the breast cancer cells. Methods: The MICA exons 2~6 of 85 breast cancer patients and those of 100 healthy blood donors were determined by PCR-SBT. Expression level of mMICA and sMICA of patients with different malignant degree of breast cancer were examined by immunohistochemistry, Western blot and ELISA technology,respectively. we synthesized of MICA RNA interference fragment using the chemical method, and transfected them into human breast cancer cell line MDA-MB-231 by liposome, killing effect of NK cells on breast tumor cells were examined by LDH method. Results: In breast cancer patients,the allele frequencies of MICA*010:01((27.6%vs12%,Pc<0.05,OR=2.802[CI:1.628-4.823])) and MICA*049(10%vs2.0%,Pc<0.05,OR=5.444,[CI:1.795-16.513]) were higher than those of controls, whereas the allele frequency of MICA*008:01 was lower than those of the controls(17.1%vs36%,Pc<0.05,OR=0.366,[CI:0.223-0.599]). Results showed that the expression level of mMICA was negatively correlated with malignant degree of breast cancer(P<0.05). However, there was positive correlation between the expression level of sMICA and tumor malignant degree(P<0.05). We found that the killing effect of NK cells on breast tumor cells with low MICA expression was reduced. Conclusions:The results reveal that MICA*010:01,MICA*049 are more likely to be susceptible alleles for breast cancer,while MICA*008:01 a potential protective allele to pathogenesis of breast cancer. The expression level of mMICA was negatively correlated with malignant degree of breast cancer. However, there was positive correlation between the expression level of sMICA and tumor malignant degree.The down-regulated expression of MICAcan decrease the anti-tumor effect of NK cells.