Abstract
SCC-S2/GG2-1/NDED is a recently discovered antiapoptotic molecule induced by the activation of the transcription factor NF-κB. Here we have examined a role of SCC-S2 in cell growth regulation in vitro and in vivo. Western blotting using an antipeptide antibody revealed endogenous SCC-S2 as a ∼21 kDa cytosolic protein in human breast cancer cells (MDA-MB 231) and renal carcinoma cells (RCC-RS). The immunofluorescence detection method showed the cytosolic localization of FLAG-tagged human SCC-S2 in COS-1 transfectants. MDA-MB 435 human cancer cells stably transfected with the FLAG-tagged SCC-S2 cDNA exhibited increased growth rate as compared to control vector transfectants, as measured by the cell viability (>twofold; n=3; P<0.005) and thymidine-labeling procedures (∼sixfold; n=3; P<0.0001). SCC-S2 transfectants also displayed an increase in cell migration in collagen I as compared to control transfectants (∼twofold; n=3; P<0.005). In athymic mice, SCC-S2 transfectants showed significantly enhanced tumor growth as compared to control transfectants (mean tumor volumes, day 16: control, 56.86±19.82 mm3; SCC-S2, 127.54±18.78 mm3; n=5; P<0.03). The examination of a limited number of clinical specimens revealed higher expression levels of SCC-S2 protein in certain human tumor tissues as compared to the matched normal adjacent tissues. Taken together, the present studies demonstrate SCC-S2 as a novel oncogenic factor in cancer cells.
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Acknowledgements
MDA-MB 231 and MDA-MB 435 human cancer cells were obtained from the Tissue Culture Shared Resource facility of the Lombardi Cancer Center, Georgetown University Medical Center. Mice studies were performed at the Research Resource Facility of the Division of Comparative Medicine, Georgetown University Medical Center. This study was supported by grants from the National Institutes of Health (P01 CA74175) and NeoPharm, Inc.
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Kumar, D., Gokhale, P., Broustas, C. et al. Expression of SCC-S2, an antiapoptotic molecule, correlates with enhanced proliferation and tumorigenicity of MDA-MB 435 cells. Oncogene 23, 612–616 (2004). https://doi.org/10.1038/sj.onc.1207123
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DOI: https://doi.org/10.1038/sj.onc.1207123
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