Small
ubiquitin-like modifier (
SUMO) proteins are involved in a variety of cellular processes. Alterations in SUMO conjugation have been implicated in several human diseases, including
cancer. Although the main cause of failure in
cancer treatment is the development of drug resistance by
cancer cells, the mechanisms of drug resistance are not fully understood.
SUMO proteins are thought to play roles in various cellular pathways, but no studies have as yet compared the expression of the different
SUMO proteins in chemosensitive and
drug-resistant
cancer cells. To determine the relationship between
protein sumoylation and drug resistance, the expression of various SUMO
isoforms has been studied and compared in the HL-60 cell line (a model for leukemic cells) and in HL-60RV cells (resistant to
vincristine). Co-immunostaining of cells by anti-SUMO
antibodies and
antibodies against various nuclear subdomains has been examined by an advanced type of bioimaging analysis. Whereas SUMO-2/3 co-localizes exclusively with nuclear bodies containing
promyelocytic leukemia protein in both cell types, SUMO-1 has also been seen in nucleolar regions of HL-60, but not in HL-60RV, cells. In HL-60 cells, SUMO-1 occurs adjacent to, but not co-localized with, the nucleolar marker
fibrillarin. Western blot analysis has revealed higher levels of free SUMO and sumoylated products in
drug-resistant cells and the presence of specific SUMO-1 conjugates in
drug-sensitive HL-60 cells, possibly consistent with a specific nucleolar signal. Shortly after the induction of
ethanol and oxidative stress, HL-60RV, but not HL-60, cells show increased accumulation of high-molecular-weight SUMO-2/3 conjugates. Thus, SUMO-1 probably has a specific role in the nucleoli of HL-60 cells, and the alteration of sumoylation might be a contributing factor in the development of drug resistance in
leukemia cells.