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BMP6

Bone morphogenetic protein 6 (BMP6) is an important regulator of cell growth, differentiation and apoptosis in various types of tumor. In breast cancer, it was considered as a tumor suppressor. Our previous study also confirmed that BMP6 was a critical regulator of breast cancer drug resistance. However, little is known about how its expression is regulated and its mechanisms in breast cancer drug resistance. In the present study, we assessed the DNA methylation regulation of BMP6 based on the presence of a large CpG island in the BMP6 gene promoter. Quantitative DNA methylation analyses showed a significantly increased DNA methylation level in the drug-resistant cell line MCF-7/ADR compared to their parental cells MCF-7. Moreover, the drug-resistant cell line MCF-7/ADR showed an EMT phenotype confirmed by morphology and the expression of EMT marker gene. MCF-7 cells transfected with BMP6-specific shRNA vector also showed an EMT phenotype. The MCF-7/ADR cells treated with the recombinant BMP6 proteins reversed their EMT phenotype. These data indicated that hypermethylation modifications contributed to the regulation of BMP6 and induced an EMT phenotype of breast cancer during the acquisition of drug resistance.

The pleomorphic adenoma is the most frequently encountered tumor of the salivary glands, representing between 45% and 75% of the total number of the tumors of the salivary glands. According to the literature, there are many studies on the immunohistochemical aspects of the myoepithelial cells, present in the pleomorphic adenoma of the salivary gland. A big diversity of mono and polyclonal antibodies, such as the cytokeratins, muscular proteins and other markers, has been used. In our study, we investigated the immunohistochemical aspect of bone morphogenetic protein 6 (BMP6) marker concerning 15 cases of pleomorphic adenomas of the salivary glands. In the immunohistochemical study, we used the paraffin blocks that served for obtaining the sections necessary for the classical histopathological processing by means of the usual stainings. The immunohistochemical study used the enzymatic detection and the LSAB 2 (Labeled Streptavidin-Biotin 2) System technique as the working method. In order to underline the process of epithelial-mesenchymal transition, we also used double sequential immunohistochemical reactions. By the use of the BMP6 marker, we intended to evaluate the reactivity of the various tumor components in the pleomorphic adenomas of the salivary gland, for this marker, taking into consideration its possible involvement in the process of the epithelial-mesenchymal transition. The maximum reactivity for BMP6 was recorded at the level of the normal, excretory, intratubular units, in the luminal cells of the proliferative ductal units, in the myxoid matrix, the cytoplasm of the myxoid stellate cells and the plasmacytoid matrix and the cytoplasm of the chondroid lacunar cells. Some of the cells belonging to the solid, proliferative areas, some of the abluminal cells, that are part of the proliferative ductal units and certain myxoid stellate or plasmocytoid cells contain the S100 protein, which would indicate the existence of some processes of mesenchymal epithelial/myoepithelial transdifferentiation in the development of this type of salivary tumor. The BMP6 expression is specific to the serous acini salivary cells, which are the most specialized epithelial salivary gland cells. The study demonstrated that the mesenchymal epithelial/myoepithelial potential of transdifferentiation of the luminal cells that make up the proliferative units is certified by the immunohistochemical expression of some BMP6 purely mesenchymal protein cells.