Increased galectin-7 gene expression in lymphoma cells is under the control of DNA methylation.
Recent studies have reported that elevated levels of galectin-7 in different types of cancer. The mechanisms underlying its abnormal regulation in cancer cells remain, however, unknown. Here, we have examined the relationship between galectin-7 and p53, a gene previously associated with upregulation of galectin-7. While RNA and protein analyses revealed a consistent and irreversible upregulation of galectin-7 throughout progression of lymphoma, no correlation with p53 was found. In fact, most of the lymphoma cell lines expressing high levels of galectin-7 did not express any detectable level of p53, although expressed p21(Waf1/Cip1) gene following doxorubicin treatment, indicating that p53 was functional in these cells. Methylation-specific polymerase chain reaction (MS-PCR) analyses rather suggested that galectin-7 expression was associated with changes in DNA methylation. This conclusion was supported by data using demethylating agent 5-aza-dC. Furthermore, disruption of the DNA methylases dnmt1 and dnmt3a induced galectin-7. Collectively, our data suggest that abnormal expression of galectin-7 in lymphoma cells is not dependent on p53, but is rather associated with DNA hypomethylation.
Demers
Mélanie
M
INRS-Institut Armand-Frappier, Laval, Quebec, Canada.
Couillard
Julie
J
Giglia-Mari
Giuseppina
G
Magnaldo
Thierry
T
St-Pierre
Yves
Y
D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics / Q000378:metabolism; D019175:DNA Methylation; D037161:Galectins / Q000235:genetics*; D015870:Gene Expression; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D008223:Lymphoma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D037161:Galectins; C092525:LGALS7 protein, human; D016159:Tumor Suppressor Protein p53; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; C000619380:DNMT1 protein, human; C112218:TRDMT1 protein, human