ABSTRACT
Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that account for about 2% of gastric tumors. Metallothioneins (MTs) are multifunctional proteins associated with carcinogenesis and known to be coded by 10 functional MT genes. This study evaluated MT mRNA and protein expression in GISTs and compared the expression levels with gastric carcinomas. An immunohistochemical study of MT protein expression was performed in 15 GISTs (specifically located in the stomach) and 38 early stage gastric carcinomas. The percentage of cells stained and intensity of staining were determined. MT-2A mRNA expression was investigated in 6 GISTs and 6 early stage gastric carcinoma patients. All GISTs displayed positive nuclear immunostaining, with most GISTs having predominantly mildly stained nuclei (93.3%). On the other hand, 37 out of 38 gastric carcinoma cases were positively stained for nuclear MT with 24 cases (63.2%) exhibiting predominantly mild nuclear staining, 7 cases (18.4%) moderate nuclear staining, and 6 cases (15.8%) strong nuclear staining. Nuclear MT expression was found to be significantly lower in GIST samples when compared with gastric carcinoma tissues based on the percentage stained and immunoreactive score. We then established that the MT-2A gene transcript was the most abundant MT isoform in MKN28 gastric cancer cells and analyzed its expression in GIST and gastric carcinoma tissues. We found that GISTs had significantly lower MT-2A mRNA levels than gastric carcinoma tissues. Lower MT-2A gene expression and nuclear MT protein expression in GISTs when compared with gastric carcinomas may reflect their different underlying biology and divergent histogenesis.
Subject(s)
Adenocarcinoma/metabolism , Biomarkers, Tumor/metabolism , Gastrointestinal Stromal Tumors/metabolism , Metallothionein/metabolism , Stomach Neoplasms/metabolism , Adenocarcinoma/pathology , Cell Line, Tumor , Cell Nucleus/metabolism , Gastrointestinal Stromal Tumors/pathology , Humans , Neoplasm Staging , RNA, Messenger/metabolism , Stomach Neoplasms/pathologyABSTRACT
Heat shock proteins (HSPs) are evolutionarily conserved molecules and play important roles in fundamental cellular processes. They serve as molecular chaperones and hence provide a protective function in ensuring cell survival and repair of cellular damage after a stressful stimulus. This paper summarizes the current knowledge about the different roles of HSPs in aging and disease, focusing on the neurodegenerative disorders of Alzheimer's marks disease, Parkinson's disease, Huntington's marks disease, and prion disease.
