The Relationship Of Cyclin A1 Gene Hypermethylation In Promoter Region And Oncogenesis, Metastasis Of Breast Carcinoma

Background and Objective:The incidence of cancer is a multi-phase, involving complex genetic and epigenetic processes. In recent years, the role of DNA methylation in occurrence and development of cancer is more and more important .CpG island hypermethelation of tumor suppressor genes is considered a new mechanism for inactivation.There is a higher rate of methylation for Cyclin A1 gene in a variety of malignant tumors. Breast cancer is one of the most common malignant tumors for women and it is the second cause of death in women which is died of cancer(15%),the first cause of death is lung cancer. In recent years, its incidence increased year by year. Therefore, the domestic and international research on breast cancer has become a hot area of female cancer.CCNA1,the cycin A1 is involved in cell cycle regulation;it regulate DNA synthesis and promote cell into mitosis.It can interact with cyclin-dependent kinases-2 and combine with important cell cycle factors,such as Rb family proteins, transcription factor E2F-1, P21 family protein etc.Study confirmed that CCNA1plays an important role in prostate invasion and metastasis,it mainly increases MMPs, UpA, VEGF expression to promote tumor invasion and metastasis. Because of few studies in breast cancer, this paper aims to detect CCNA1 gene promoter methylation in breast cancer to explore the relationship of tumor metastasis. Methods: (1) The tumor specimens and matched normal breast tissue specimens from 95 patients with breast cancer were used for the extraction of DNA by Qiagen Formalin-Fixed and Parrffin-Embedded procedure;(2) Methylation change in the promoter region of CCNA1 genes was determined by using methylation-sensitive restriction endonuclease cut-PCR(.3)The fragment was amplified by nested-PCR ,the amplified fragment was used for DNA sequencing.(4)1.5% Agarose gel electrophoresis was used for test the results.Results:(1) The positive rate of gene promoter hypermethylation of CCNA1 was 90.9% (86/95) in tumor tissue,as compared to 10.5%(10/95) in normal breast tissue,respectively.The positive rate was significantly higher in tumor tissue than in normal breast tissue .(2) Breast cancer with Cyclin A1 gene promoter hypermethelation was significantly correlated with lymph node metastasis(P=0.019) and distant metastasis(P=0.032) .(3)The Cyclin A1 gene promoter mutation was not found in breast cancer.Conclusion:CCNA1 hypermethylation might be involved in tumorigenesis of breast cancer and it was correlated with lymph node metastasis, which may play an important role in pathogenesis of breast cancer.