Hypermethylation and Expression of DLCl Gene in Sporadic Breast Cancer and Breast Benign Lesions Tissues

ObjectiveTo study the methylation status of DLC1 gene promoter regions and the expression level of DLC1 protein in the development of sporadic breast cancer (SBC), and to research the epigenetics of aberrant DLC1 gene in SBC. Methods Methylation specific polymerase chain reaction (MSP) was used to study the methylation status of DLC1 promoter regions in 42 samples of SBC, 14 cases of breast atypital ductal hyperplasia (BADH), 20 cases of breast adenosis (BA) and 5 samples of peripheral lymphocytes from healthy adult women.The expression of DLC1 protein was detected by immunohistochemistry staining (EnVision method). Results We found DLC1 promoter methylation rate was 38.1% in SBC tissues.In BADH tissues，(35.7%) showed aberrant methylation of DLC1 gene promoter.While in the tissues of BA and 5 cases healthy adult women's peripheral lymphocytes， no methylation of DLC1 gene was found.In 42 cases of SBC， 26 cases (61.91%) showed loss expression of DLC1 protein and 16 cases (38.10%) showed reduction expression.In 14 BADH tissues， 6 cases (42.86%) showed negative expression of DLC1 protein, 8 cases (57.14%) showed reduced expression.No reduced or loss expression of DLC1 protein was found in BA tissues.In the 16 cases of DLC1 methylated SBC tissues, 14 cases showed no expression of DLC1 protein, another 2 cases showed weakly express DLC1 protein.In the 5 cases of DLC1 methylated BADH tissues, 3 cases negatively express, 2 cases showed reduced expression of DLC1 protein.Statistical analysis showed the methylation rates of DLC1 gene in SBC and BADH tissues were higher than that of BA.The difference in the three groups had statistical significance (P<0.01).While the methylation rates of DLC1 gene between SBC and BADH tissues were no difference.The expression rates of DLC1 protein in SBC and BADH tissues were lower than BA.And the expression rate of DLC1 protein in SBC is significantly lower than that of BADH.The positive intensities of DLC1 protein of DLC1 unmethylated group is higher than that of DLC1 methylated group(P<0.01). Conclusion The promoter methylation of DLC1 gene is an early event in the development of SBC and may contribute to the reduction or loss expression of DLC1 protein.The promoter methylation of DLC1 gene may play an important biological role in breast carcinogenesis.