Effects of DNA methylation on galectin-3 expression in pituitary tumors.
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.
Ruebel
Katharina H
KH
Department of Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Jin
Long
L
Qian
Xiang
X
Scheithauer
Bernd W
BW
Kovacs
Kalman
K
Nakamura
Nobuki
N
Zhang
Heyu
H
Raz
Avraham
A
Lloyd
Ricardo V
RV
D000236:Adenoma / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018899:CpG Islands; D019175:DNA Methylation; D037502:Galectin 3 / Q000096:biosynthesis* / Q000235:genetics; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D010911:Pituitary Neoplasms / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic
D037502:Galectin 3