5 results on '"Seftor, Elisabeth A"'
Search Results
2. Global Demethylation of Rat Chondrosarcoma Cells after Treatment with 5-Aza-2′-Deoxycytidine Results in Increased Tumorigenicity
- Author
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Hamm, Christopher A., Xie, Hehuang David, Costa, Fabricio F., Vanin, Elio F., Seftor, Elisabeth A., Sredni, Simone T., Bischof, Jared, Wang, Deli, Bonaldo, Maria F., Hendrix, Mary J. C., Soares, Marcelo B., Hamm, Christopher A., Xie, Hehuang David, Costa, Fabricio F., Vanin, Elio F., Seftor, Elisabeth A., Sredni, Simone T., Bischof, Jared, Wang, Deli, Bonaldo, Maria F., Hendrix, Mary J. C., and Soares, Marcelo B. more...
- Abstract
Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells. more...
- Published
- 2009
- Full Text
- View/download PDF
Catalog
3. Global Demethylation of Rat Chondrosarcoma Cells after Treatment with 5-Aza-2′-Deoxycytidine Results in Increased Tumorigenicity
- Author
-
Hamm, Christopher A., Xie, Hehuang David, Costa, Fabricio F., Vanin, Elio F., Seftor, Elisabeth A., Sredni, Simone T., Bischof, Jared, Wang, Deli, Bonaldo, Maria F., Hendrix, Mary J. C., Soares, Marcelo B., Hamm, Christopher A., Xie, Hehuang David, Costa, Fabricio F., Vanin, Elio F., Seftor, Elisabeth A., Sredni, Simone T., Bischof, Jared, Wang, Deli, Bonaldo, Maria F., Hendrix, Mary J. C., and Soares, Marcelo B. more...
- Abstract
Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells. more...
- Published
- 2009
- Full Text
- View/download PDF
4. Global Demethylation of Rat Chondrosarcoma Cells after Treatment with 5-Aza-2′-Deoxycytidine Results in Increased Tumorigenicity
- Author
-
Hamm, Christopher A., Xie, Hehuang David, Costa, Fabricio F., Vanin, Elio F., Seftor, Elisabeth A., Sredni, Simone T., Bischof, Jared, Wang, Deli, Bonaldo, Maria F., Hendrix, Mary J. C., Soares, Marcelo B., Hamm, Christopher A., Xie, Hehuang David, Costa, Fabricio F., Vanin, Elio F., Seftor, Elisabeth A., Sredni, Simone T., Bischof, Jared, Wang, Deli, Bonaldo, Maria F., Hendrix, Mary J. C., and Soares, Marcelo B. more...
- Abstract
Abnormal patterns of DNA methylation are observed in several types of human cancer. While localized DNA methylation of CpG islands has been associated with gene silencing, the effect that genome-wide loss of methylation has on tumorigenesis is not completely known. To examine its effect on tumorigenesis, we induced DNA demethylation in a rat model of human chondrosarcoma using 5-aza-2-deoxycytidine. Rat specific pyrosequencing assays were utilized to assess the methylation levels in both LINEs and satellite DNA sequences following 5-aza-2-deoxycytidine treatment. Loss of DNA methylation was accompanied by an increase in invasiveness of the rat chondrosarcoma cells, in vitro, as well as by an increase in tumor growth in vivo. Subsequent microarray analysis provided insight into the gene expression changes that result from 5-aza-2-deoxycytidine induced DNA demethylation. In particular, two genes that may function in tumorigenesis, sox-2 and midkine, were expressed at low levels in control cells but upon 5-aza-2-deoxycytidine treatment these genes became overexpressed. Promoter region DNA analysis revealed that these genes were methylated in control cells but became demethylated following 5-aza-2-deoxycytidine treatment. Following withdrawal of 5-aza-2-deoxycytidine, the rat chondrosarcoma cells reestablished global DNA methylation levels that were comparable to that of control cells. Concurrently, invasiveness of the rat chondrosarcoma cells, in vitro, decreased to a level indistinguishable to that of control cells. Taken together these experiments demonstrate that global DNA hypomethylation induced by 5-aza-2-deoxycytidine may promote specific aspects of tumorigenesis in rat chondrosarcoma cells. more...
- Published
- 2009
5. p53-independent NOXA induction overcomes apoptotic resistance of malignant melanomas
- Author
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Qin, Jian-Zhong, Stennett, Lawrence, Bacon, Patricia, Bodner, Barbara, Hendrix, Mary, Seftor, Richard, Seftor, Elisabeth, Margaryan, Naira, Pollock, Pamela, Curtis, Amy, Trent, Jeffrey, Bennett, Frank, Miele, Lucio, Nickoloff, Brian, Qin, Jian-Zhong, Stennett, Lawrence, Bacon, Patricia, Bodner, Barbara, Hendrix, Mary, Seftor, Richard, Seftor, Elisabeth, Margaryan, Naira, Pollock, Pamela, Curtis, Amy, Trent, Jeffrey, Bennett, Frank, Miele, Lucio, and Nickoloff, Brian more...
- Abstract
Once melanoma metastasizes, no effective treatment modalities prolong survival in most patients. This notorious refractoriness to therapy challenges investigators to identify agents that overcome melanoma resistance to apoptosis. Whereas many survival pathways contribute to the death-defying phenotype in melanoma, a defect in apoptotic machinery previously highlighted inactivation of Apaf-1, an apoptosome component engaged after mitochondrial damage. During studies involving Notch signaling in melanoma, we observed a gamma-secretase tripeptide inhibitor (GSI; z-Leu-Leu-Nle-CHO), selected from a group of compounds originally used in Alzheimer's disease, induced apoptosis in nine of nine melanoma lines. GSI only induced G2-M growth arrest (but not killing) in five of five normal melanocyte cultures tested. Effective killing of melanoma cells by GSI involved new protein synthesis and a mitochondrial-based pathway mediated by up-regulation of BH3-only members (Bim and NOXA). p53 activation was not necessary for up-regulation of NOXA in melanoma cells. Blocking GSI-induced NOXA using an antisense (but not control) oligonucleotide significantly reduced the apoptotic response. GSI also killed melanoma cell lines with low Apaf-1 levels. We conclude that GSI is highly effective in killing melanoma cells while sparing normal melanocytes. Direct enhancement of BH3-only proteins executes an apoptotic program overcoming resistance of this lethal tumor. Identification of a p53-independent apoptotic pathway in melanoma cells, including cells with low Apaf-1, bypasses an impediment to current cytotoxic therapy and provides new targets for future therapeutic trials involving chemoresistant tumors. more...
- Published
- 2004
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