Article

Effects of DNA methylation on galectin-3 expression in pituitary tumors.

Department of Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Cancer Research (impact factor: 7.86). 03/2005; 65(4):1136-40. DOI:10.1158/0008-5472.CAN-04-3578 pp.1136-40
Source: PubMed

ABSTRACT Galectin-3 (Gal-3), a beta-galactoside-binding protein is expressed in a specific cell-type manner in pituitary tumors. Here we questioned the mechanism of Gal-3 expression in pituitary tumors, by using methylation-specific PCR and DNA sequence analyses to analyze the methylation status of the promoter region of the LGALS3 gene. DNA analysis of a human pituitary tumor, breast carcinoma cell lines, and thyroid carcinoma cell lines showed that in cells expressing Gal-3 protein, the LGALS3 gene was unmethylated, whereas in Gal-3 null cells, the promoter of the LGALS3 gene was methylated. Treatment of cells with 30 mumol/L 5-aza-2'-deoxycytidine induced Gal-3 mRNA and protein expression. Among pituitary tumors, 30% (7/23), mainly in follicle-stimulating hormone/luteinizing hormone-producing (38%) and null cell (57%) adenomas, the promoter of the LGALS3 was found to be methylated and silenced, although prolactin- and adrenocorticotropic hormone-producing tumors, which were unmethylated, expressed the Gal-3 protein. These results show for the first time that Gal-3 expression is regulated in part by promoter methylation in pituitary as well as in other tumors. Because it is functionally involved in cancer progression and metastasis, Gal-3 may serve as a possible therapeutic target in the treatment of pituitary tumors.

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Keywords

adrenocorticotropic hormone-producing tumors
 
beta-galactoside-binding protein
 
breast carcinoma cell lines
 
cancer progression
 
DNA analysis
 
DNA sequence analyses
 
follicle-stimulating hormone/luteinizing hormone-producing
 
Gal-3 expression
 
Gal-3 null cells
 
Gal-3 protein
 
human pituitary tumor
 
LGALS3 gene
 
methylation status
 
methylation-specific PCR
 
null cell
 
pituitary tumors
 
possible therapeutic target
 
protein expression
 
specific cell-type manner
 
thyroid carcinoma cell lines