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 hi.-h 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. (C) 2009 Elsevier Inc. All rights reserved.