ABSTRACT
Interest in epigenetics has gained substantial momentum as a result of their identified role in the regulation of tumor progression as well as their ability to pharmacologically target genes. Pituitary neuroendocrine tumors (PitNETs) tend to be inactivated via epigenetic modification, and although emerging evidence has suggested a role for epigenetic factors in PitNET tumorigenesis, the degree to which these factors may be targeted by new therapeutic strategies still remains poorly understood. The objective of the present study was to examine the participation of the EZH2/H3K27me3 axis in the proliferation of lactotroph tumor cells. We demonstrated that the levels of EZH2 and H3K27me3 were increased in murine experimental prolactin (PRL) tumors with respect to a control pituitary, in contrast with the low p21 mRNA levels encountered, with an H3K27me3 enrichment being observed in its promoter region in a GH3 tumor cell. Furthermore, specific EZH2/H3K27me3 axis inhibition blocked the proliferation of primary tumor cell culture and GH3 cells, thereby making it an attractive therapeutic target for PRL PitNETs.
Subject(s)
Lactotrophs , Neuroendocrine Tumors , Pituitary Neoplasms , Humans , Mice , Animals , Histones/metabolism , Lactotrophs/metabolism , Enhancer of Zeste Homolog 2 Protein/genetics , Enhancer of Zeste Homolog 2 Protein/metabolism , Cell Line, Tumor , Epigenesis, Genetic , Cell Proliferation/genetics , Pituitary Neoplasms/genetics , Neuroendocrine Tumors/geneticsABSTRACT
Axinella corrugata lectin 1 (ACL-1) was purified from aqueous extracts of the marine sponge, Axinella corrugata. ACL-1 strongly agglutinates native rabbit erythrocytes. The hemagglutination is inhibited by N-acetyl derivatives, particularly N, N', N"-triacetylchitotriose, N-acetyl-D-glucosamine, N-acetyl-D-mannosamine and N-acetyl-D-galactosamine. We investigated the capacity of biotinylated ACL-1 to stain several transformed cell lines including breast (T-47D, MCF7), colon (HT-29), lung (H460), ovary (OVCAR-3) and bladder (T24). ACL-I may bind to both monosaccharides and oligosaccharides of tumor cells, N-acetyl-D-galactosamine, and N-acetyl-D- glucosamine glycan types. The lectins are useful, not only as markers and diagnostic parameters, but also for tissue mapping in suspicious neoplasms. In addition, they provide a better understanding of neoplasms at the cytological and molecular levels. Furthermore, the use of potential metastatic markers such as lectins is crucial for developing successful tools for therapy against cancer. We observed that biotinylated ACL-I stains tumor cells and may hold potential as a probe for identifying transformed cells and for studying glycan structures synthesized by such cells.
