Abstract:
Objective To verify the existence of a regulatory pathway for breast cancer metastasis that included the genes GRP, BPAG1, and SFRP2 using biological methods and to propose the pathway based on previous research involving a multidisciplinary approach that involved biology, mathematics, and informatics.
Methods Paraffin-embedded tissue sections were obtained to determine the expressions of GRP, BPAG1, and SFRP2 genes in metastatic lesions in the lymph nodes of 70 patients with primary breast cancer using immunohistochemistry. Breast cancer MCF-7 cells were cultured. Real-time polymerase chain reaction and Western blot were used to determine the mRNA and the protein levels, respectively, of both BPAG1 and SFRP2, following the up-regulation or down-regulation of GRP expression caused by the transfection of GRP or GRP-shRNA (small hairpin RNA), respectively, into the MCF-7 cells.
Results The expressions of the GRP, BPAG1, and SFRP2 genes were significantly higher in the lymph node tissues than in the corresponding primary breast cancer tissues. The mRNA levels and protein expression of BPAG1 in MCF-7 cells where GRP was either up-regulated or down-regulated were higher and lower, respectively, compared with the untreated controls. Moreover, the mRNA levels of SFRP2 followed a trend similar to that of GRP.
Conclusion A possible signal transduction pathway regulated by the GRP, BPAG1, and SFRP2 genes may play an important role in the metastasis of breast cancer.
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