Homeobox Gene MSX1is Methylated In Breast Cancer And Can Function As A Tumor Suppressor

Objective: Both epigenetic and genetic alterations are involved intumorigenesis. The methylation of tumor suppress genes can induce theinactivation of gene functions thus plays an important role incarcinogenesis. This article is aim to investigate the role of a novelcandidate tumor suppressor gene MSX1in breast carcinogenesis and toidentify the epigenetic mechanism underlying for its inactivation.Methods：Semi-quantitative reverse-transcription (RT-PCR) was usedto detect MSX1expression in various normal adult tissues and9breatscancer cell lines. Methylation-specific PCR (MSP) was used for examingMSX1promoter methylation in breast cancer cell lines before and after thetreatment of pharmacological demethylation agent5’-aza-2’-deoxycytidineand trichostatin A（TSA）. With the ectopic expression of MSX1, weperformed colony formation for exploring the function on growth of tumorcells in vitro.Results：Frequent promoter methylation and silencing of MSX1wasdetected in78%（7/9）and67%（6/9）of breast cancer cells linesrespectively. Pharmacological demethylation restored its expression,indicating a direct epigenetic mechanism. Ectopic expression of MSX1 resulted in significant inhibition of colony formation in MB468breastcancer cell.Conclusion： Our study indicated that homeobox gene MSX1,epigenetically inactivated by promoter CpG methylation, which can berestored by demethylation agents, exerted tumor-suppressive functions inbreast carcinoma.