Differential expression patterns of SUMO proteins in HL-60 cancer cell lines support a role for sumoylation in the development of drug resistance |
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Authors: | Margarita Vigodner Jeffrey H Weisburg Vibha Shrivastava Rebecca A Marmor Jennifer Fathy Nolan Skop |
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Institution: | (1) Stern College for Women, Department of Biology, Yeshiva University, 245 Lexington Avenue, New York, NY 10016, USA |
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Abstract: | 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.
The author thanks Stern College for Women, Yeshiva University and the Joseph Alexander Foundation for supporting this research
project. |
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Keywords: | SUMO proteins Drug resistance Leukemia HL-60 Cell lines Human |
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