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Study The Expression Of MTA1in Different Cell Lines And Liver Cancer Tissues

Posted on:2012-11-16Degree:MasterType:Thesis
Country:ChinaCandidate:Z W LiFull Text:PDF
GTID:2234330395981686Subject:Microbiology
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MTA, a tumor metastasis-related gene family, is firstly discovered in breast cancer, which has been identified3categories (MTA1, MTA2, MTA3) and6subtypes (MTA1, MTA1s, MTA-ZG29p, MTA2, MTA3and MTA3L). MTA1, MTA2and MTA3were considered to be a part of nuclear remodeling and deacetylase complexs (NuRD), and play biological roles by influencing chromatin to adjust the replicationand regulation of histone deacetylase. Recently, many studies found that MTAl was closely associated with invasion and metastasis of human cancers, such as stomach, esophagus, and lung cancer. Although research suggests that MTA1has been promoting a variety of tumor invasion and metastasis is a key factor, but studies in the liver metastasis is very small.To investigate the MTA1s potential roles in liver cancer metastasis, we preform this reseach. In current study, we measured MTAl expression in several cell lines by semi-quantitative RT-PCR and real-time RT-PCR. The result showed that the expression of MTA1in HepG2and SSMC-7721, two liver cancer cell lines were higher than L02, a normal liver cell lines. This meaned that MTA1was expressed in cancer cell lines. Meanwhile, the MTA1expression was measured in clinical samples by RT-PCR. The reuslt showed that its expression in normal liver tissue and adjacent tissue were lower than liver cancer, and it in metastatic liver cancer was the highest. All those results implied that MTA1was associated with liver cancer formation and metastatic. Furthermore, to investigate the pathway of MTA1in liver cancer, we screened cancer associated signal transcript factors by Mercury pathway profiling system. The results showed that oncogene RB expression was incresed by MTA1, but the expression of tumor suppressor gene p53was decreased by MTA1. Importantly, all those genes were regulated in dose-dependent manner.Our fundings suggested that MTA1may play critical roles in formation and metastatic of liver cancer. This research provied a new insight to understanding the relationship between MTA1and liver cancer metastatic, however, the cellular and molecular mechanisms under this process still need further study.From experimental cell lines and two samples of clinical cases, using RT-PCR method to detect analysis of MTA1expression in liver cancer, liver cancer was found in the cell line HepG2and SSMC-7721cells in the liver from the level of The sources of higher than normal liver cells L02, at the level of clinical samples, expression of metastatic liver cancer than non-metastatic liver cancer and adjacent tissues. The results form signaling pathways screening analysis of tumor-associated transcription factor showed that MTA1can significantly enhance the expression of RB gene, and inhibited tumor suppressor gene p53. These results suggest that MTA-1in the development of liver cancer and metastatic process may play an important role.MTA1metastasis of liver cancer occurrence and the molecular mechanism is still not conclusive. Existing research shows that the role of MTA1protein may be largely because of its histone deacetylase (HDACs) to form NuRD (nucleosomeremodeling and histone deacetylase) complex, to promote nucleosome remodeling and histone deacetylase activity, thereby inhibiting the transcription of certain tumor suppressor gene expression. In addition, MTA1, and some can also be directly associated with apoptosis mediated by binding to its regulation of apoptosis and lead to the microfilament system assembly cytokeratin negative, significantly reduced the stability of the cytoskeleton, leading to tumor and metastasis. This article attempts to cause the signaling pathway from the MTA1to explore aspects of the mechanism for the development of tumors and found that MTAl can significantly enhance the expression of RB oncogenes, tumor suppressor gene p53on the contrary inhibited.MAT1gene as a channel and signal transduction and gene regulation of the metastasis-related genes, may occur in the development of liver cancer also plays a key role, with the MTAl expression in different tumors and the role of research, will further reveal the the mechanism of tumor invasion and metastasis, may also make tumor MTA1may be physiological processes such as development and transfer of the indicators, will be the early diagnosis of metastasis and tumor immunotherapy targets. Therefore, spectral analysis of its expression, and then understand its mechanism of action, HCC will further clarify the cellular and molecular mechanisms, but also a new strategy for the treatment of liver cancer provides theoretical support.
Keywords/Search Tags:MTA1, Liver cancer, Metastatic, Signaling pathway, P53, RB
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