Studies On Expression And Epigenetic Mechanisms Of MARVELD1 In Breast Cancer Lines

Cancer has become one of the serious diseases that have great harmful to human health. The epigenetic regulations of oncogenes, tumor suppressors and other tumor-related genes play important roles in tumorigenesis and progression. MARVELD1 is a novel tumor suppressor gene, which was firstly found in the study of molecular mechanism of tumorigenesis and metastasis in our lab. It located on the human chromosome 10q24.2. The expression of MARVELD1 was found in multiple normal tissues in the early study, and the results of Cancer Profiling Array showed that the expression level of MARVELD1 was down-regulated in some tumors (breast cancers, kidney cancers,lung cancers and so on).To further study the expression and epigenetic regulating mechanisms of MARVELD1 in human breast cancer cell lines, Real-time PCR was performed to analyze the endogenetic expression of MARVELD1 in 11 human breast cancer cell lines and MCF-10A as control which is a normal cell line. The results showed that the expression of MARVELD1 in SK-BR-3 is distinct lower than that in MCF10A. On the basis of the result, Real-time PCR and Western blot analysis was performed in SK-BR-3 cells treated with 1.0, 5.0μM 5-Aza-CdR (Sigma, MO, USA) for 24h/48h with changing of 5-Aza-CdR and medium every 24h, the result showed that the expression of MARVELD1 was up-regulated, and it suggested that DNA methylation plays an important role in regulating the expression of MARVELD1. In addition, the expression of MARVELD1 changed both in RNA level and in protein level in SK-BR-3 cells treated by 5-Aza-CdR and 100μM TSA, which implied that acetylation had some effect on regulating the expression of MARVELD1.This research suggested that the expression of MARVELD1 varied notably in hunman breast cancer cell lines, and which is regulated by DNA methylation and acetylation. This study could have great favour of recognizing the fuctions of MARVELD1 completely, and support some theorical basis in elucidating epigenetic regulating and tumor suppressor mechanisms of MARVELD1.