Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acid beta-glucosidase (beta Glc) is a housekeeping enzyme whose expression is ubiquitous, but differs greatly according to tissue of origin. Expression of a reporter gene under the control of a 622 bp fragment of the beta Glc promoter correlated roughly with the relative amount of beta Glc mRNA detected in five different cell lines, suggesting that elements within this region play a role in determining differential expression of the beta Glc gene. Experiments using deletion mutants revealed that differential expression of beta Glc is not due to the presence of promoter elements that are active in only certain cell types, but rather due to subtle changes in the magnitude of the effect of the different elements. Strikingly, regulatory elements located upstream of the TATA box are dispensible in several cell types, whereas elements located within exon 1 of the beta Glc gene are essential for reporter gene expression in cultured cells. At least two exon 1 elements regulate mRNA levels, and one double stranded probe containing exon 1 sequences binds a factor present in extracts from HeLa and glioblastoma cells. Additionally, at least two of the exon 1 elements act in an orientation-independent fashion. Thus, it is likely that at least a subset of the exon 1 elements act as transcriptional enhancers.
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PMID:Regulation of the human acid beta-glucosidase promoter in multiple cell types. 789 61

Acid beta-glucosidase (beta Glc) activity and mRNA levels were measured in several human cell lines, and found to vary over 50-fold. A comparison between relative levels of beta Glc enzyme and mRNA levels revealed three patterns. The first group, including epithelial, lymphoblast, histiocyte, glioblastoma and astrocytoma cell lines, showed a direct relationship between relative levels of mRNA and enzyme activity, indicating that mRNA levels play an important role in determining enzyme activity. The second group, including fibroblast, promyelocyte and neuroglioma cell lines, also showed a direct relationship between beta Glc enzyme and mRNA levels within this group, but had enzyme activities that were approximately sixfold higher than expected, when compared with enzymes within the first group. The third pattern was exhibited by a single monocyte cell line, which showed high levels of beta Glc mRNA, but only intermediate levels of enzyme activity. These results suggest that although beta Glc mRNA levels play a major role in regulating beta Glc activity, other mechanisms also influence enzyme levels in certain cell lines. These results also demonstrate the importance of examining several different cell types when considering mechanisms of housekeeping gene regulation. Additionally, culturing cells in the presence of the beta Glc-specific inhibitor, conduritol-B-epoxide, did not affect beta Glc mRNA levels, and cells derived from normals had levels of beta Glc mRNA comparable to those from Gaucher disease patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of expression of the gene encoding human acid beta-glucosidase in different cell types. 850 Jul 68