| Invasion and metastasis are the major causes of mortality in malignant tumors patients, which are regulated by many related genes. Many newly found metastasis suppressor genes have very close relationship with the development and metastasis of malignant tumor. The rat metastasis associated gene 1 (MTA1) was originally identified by differential cDNA screening using adenocarcinoma cell lines with high metastatic potential by Yasushi Toh in 1994. To data, MTA is a gene family, and there are three different known genes (MTA1, MTA2, and MTA3) and six reported isoforms (MTA1, MTA1s, MTA1-ZG29p, MTA2, MTA3, MTA3L). MTA1, MTA2, and MTA3 are components of the nucleosome remodeling and deacetylation (NuRD) complex, which is associated with adenosine triphosphate-dependent chromatin remodeling and transcriptional regulation.Subsequent studies found that MTA1 plays an important role in both physiological and pathological status. Especially, MTA1 has very close relationship with the development and metastasis of malignant tumor, which has overexpressed in many human cancers including breast, lung, gastrointestinal, prostate, esophagus and other cancers. The subunit MTA1 of NuRD complex has close relationship with the subunit HADCs, showing a positive correlation with histone deacetylase, repressing the transcription of different genes by recruiting histone deacetylases onto their target genes. In addition, MTA1 converts breast cancer cells to a more aggressive phenotype by repression of the estrogen receptor (ER) a trans-activation function through deacetylation of the chromatin in the ER-responsive element of ER-responsive genes. Furthermore, MTA1 plays a certain promoting role on invasion and metastasis in different kinds of cancer cells.In the past decade, much of the attention has been focused on cancer cells metastasis mechanism of MTA1, but little attention has been paid to its physiological role. Reports indicated that MTA1 expression is not restricted to tumors; several normal mouse tissues and organs also express low levels of MTA1 especially in testis and breast, suggesting its potential function in these two tissues. In order to further address the physiological function of this histone modificator, we explored the expression of MTA1 in human and murine testes, and the results suggested its crucial role during postnatal testis development and spermatogenesis.As it is well known, the epididymis provides a continuously luminal microenvironment conducive for the transport, maturation and storage of mature spermatozoa, which are regulated by circulating and luminal androgens and to some extent by other testicular factors. In view of these facts and the crucial role during spermatogenesis of MTA1, we further study the expression of MTA1 in different segments and cell types of mouse epididymis, analyse the function during the transport, maturation and the storage of mature spermatozoa, and characterize androgen regulation, thus paving the way for a better understanding of the potential physiological role of this newly discovered molecule. The present work consists of four parts: Part 1 Expression profile of MTA1 in adult mouse tissuesPart 2 Localization analysis of MTA1 in adult mouse epididymisPart 3 Expression analysis of MTA1 during the development of mouse epididymisPart 4 Androgen regulation of MTA1 in mouse epididymisTaken together, we examined the expression pattern of mouse MTA1 in a variety of adult mouse tissues, and we found that MTA1 protein were observed on variety of tissues/cells in multiple, and then we detected the localization in epididymis, suggesting its transcript regulation role on absorption, secretion and endocytosis of epididymal epithelium. In addition, MTA1 was detected in deveoping epididymis, and the differential expression in epididymis after castration, showing MTA1 may be upregulated by androgen, which may provide a good signal for the following study on the physiological function.
|
PDF Full Text Request