A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance.
Epidemiological studies have suggested an association between selenium intake and protection from a variety of cancer. Considering this clinical importance of selenium, we aimed to identify the genes associated with resistance to selenium treatment. We have applied a previous methodology developed b...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2935366?pdf=render |
| _version_ | 1818192394441457664 |
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| author | Sevtap Savas Laurent Briollais Irada Ibrahim-zada Hamdi Jarjanazi Yun Hee Choi Mireia Musquera Neil Fleshner Vasundara Venkateswaran Hilmi Ozcelik |
| author_facet | Sevtap Savas Laurent Briollais Irada Ibrahim-zada Hamdi Jarjanazi Yun Hee Choi Mireia Musquera Neil Fleshner Vasundara Venkateswaran Hilmi Ozcelik |
| author_sort | Sevtap Savas |
| collection | DOAJ |
| description | Epidemiological studies have suggested an association between selenium intake and protection from a variety of cancer. Considering this clinical importance of selenium, we aimed to identify the genes associated with resistance to selenium treatment. We have applied a previous methodology developed by our group, which is based on the genetic and pharmacological data publicly available for the NCI60 cancer cell line panel. In short, we have categorized the NCI60 cell lines as selenium resistant and sensitive based on their growth inhibition (GI50) data. Then, we have utilized the Affymetrix 125K SNP chip data available and carried out a genome-wide case-control association study for the selenium sensitive and resistant NCI60 cell lines. Our results showed statistically significant association of four SNPs in 5q33-34, 10q11.2, 10q22.3 and 14q13.1 with selenium resistance. These SNPs were located in introns of the genes encoding for a kinase-scaffolding protein (AKAP6), a membrane protein (SGCD), a channel protein (KCNMA1), and a protein kinase (PRKG1). The knock-down of KCNMA1 by siRNA showed increased sensitivity to selenium in both LNCaP and PC3 cell lines. Furthermore, SNP-SNP interaction (epistasis) analysis indicated the interactions of the SNPs in AKAP6 with SGCD as well as SNPs in AKAP6 with KCNMA1 with each other, assuming additive genetic model. These genes were also all involved in the Ca(2+) signaling, which has a direct role in induction of apoptosis and induction of apoptosis in tumor cells is consistent with the chemopreventive action of selenium. Once our findings are further validated, this knowledge can be translated into clinics where individuals who can benefit from the chemopreventive characteristics of the selenium supplementation will be easily identified using a simple DNA analysis. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-12T00:29:48Z |
| publishDate | 2010-01-01 |
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| spelling | doaj.art-944247d88169414d8ee4489a358f82c92022-12-22T00:44:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-01-0159e1260110.1371/journal.pone.0012601A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance.Sevtap SavasLaurent BriollaisIrada Ibrahim-zadaHamdi JarjanaziYun Hee ChoiMireia MusqueraNeil FleshnerVasundara VenkateswaranHilmi OzcelikEpidemiological studies have suggested an association between selenium intake and protection from a variety of cancer. Considering this clinical importance of selenium, we aimed to identify the genes associated with resistance to selenium treatment. We have applied a previous methodology developed by our group, which is based on the genetic and pharmacological data publicly available for the NCI60 cancer cell line panel. In short, we have categorized the NCI60 cell lines as selenium resistant and sensitive based on their growth inhibition (GI50) data. Then, we have utilized the Affymetrix 125K SNP chip data available and carried out a genome-wide case-control association study for the selenium sensitive and resistant NCI60 cell lines. Our results showed statistically significant association of four SNPs in 5q33-34, 10q11.2, 10q22.3 and 14q13.1 with selenium resistance. These SNPs were located in introns of the genes encoding for a kinase-scaffolding protein (AKAP6), a membrane protein (SGCD), a channel protein (KCNMA1), and a protein kinase (PRKG1). The knock-down of KCNMA1 by siRNA showed increased sensitivity to selenium in both LNCaP and PC3 cell lines. Furthermore, SNP-SNP interaction (epistasis) analysis indicated the interactions of the SNPs in AKAP6 with SGCD as well as SNPs in AKAP6 with KCNMA1 with each other, assuming additive genetic model. These genes were also all involved in the Ca(2+) signaling, which has a direct role in induction of apoptosis and induction of apoptosis in tumor cells is consistent with the chemopreventive action of selenium. Once our findings are further validated, this knowledge can be translated into clinics where individuals who can benefit from the chemopreventive characteristics of the selenium supplementation will be easily identified using a simple DNA analysis.http://europepmc.org/articles/PMC2935366?pdf=render |
| spellingShingle | Sevtap Savas Laurent Briollais Irada Ibrahim-zada Hamdi Jarjanazi Yun Hee Choi Mireia Musquera Neil Fleshner Vasundara Venkateswaran Hilmi Ozcelik A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance. PLoS ONE |
| title | A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance. |
| title_full | A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance. |
| title_fullStr | A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance. |
| title_full_unstemmed | A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance. |
| title_short | A whole-genome SNP association study of NCI60 cell line panel indicates a role of Ca2+ signaling in selenium resistance. |
| title_sort | whole genome snp association study of nci60 cell line panel indicates a role of ca2 signaling in selenium resistance |
| url | http://europepmc.org/articles/PMC2935366?pdf=render |
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