Androgen-Regulated Transcriptional Control of Sialyltransferases in Prostate Cancer Cells
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{"title"=>"Androgen-regulated transcriptional control of Sialyltransferases in prostate cancer cells", "type"=>"journal", "authors"=>[{"first_name"=>"Koji", "last_name"=>"Hatano", "scopus_author_id"=>"14627167600"}, {"first_name"=>"Yasuhide", "last_name"=>"Miyamoto", "scopus_author_id"=>"7403108524"}, {"first_name"=>"Masaki", "last_name"=>"Mori", "scopus_author_id"=>"57192022450"}, {"first_name"=>"Keisuke", "last_name"=>"Nimura", "scopus_author_id"=>"8552031000"}, {"first_name"=>"Yasutomo", "last_name"=>"Nakai", "scopus_author_id"=>"8947726500"}, {"first_name"=>"Norio", "last_name"=>"Nonomura", "scopus_author_id"=>"7005880662"}, {"first_name"=>"Yasufumi", "last_name"=>"Kaneda", "scopus_author_id"=>"7202736982"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "scopus"=>"2-s2.0-84856698183", "pui"=>"364218414", "doi"=>"10.1371/journal.pone.0031234", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "sgr"=>"84856698183", "pmid"=>"22347453"}, "id"=>"8404f382-ceb3-34cd-9f00-7af79f15836c", "abstract"=>"The expression of gangliosides is often associated with cancer progression. Sialyltransferases have received much attention in terms of their relationship with cancer because they modulate the expression of gangliosides. We previously demonstrated that GD1a production was high in castration-resistant prostate cancer cell lines, PC3 and DU145, mainly due to their high expression of β-galactoside α2,3-sialyltransferase (ST3Gal) II (not ST3Gal I), and the expression of both ST3Gals was regulated by NF-κB, mainly by RelB. We herein demonstrate that GD1a was produced in abundance in cancerous tissue samples from human patients with hormone-sensitive prostate cancers as well as castration-resistant prostate cancers. The expression of ST3Gal II was constitutively activated in castration-resistant prostate cancer cell lines, PC3 and DU145, because of the hypomethylation of CpG island in its promoter. However, in androgen-depleted LNCap cells, a hormone-sensitive prostate cancer cell line, the expression of ST3Gal II was silenced because of the hypermethylation of the promoter region. The expression of ST3Gal II in LNCap cells increased with testosterone treatment because of the demethylation of the CpG sites. This testosterone-dependent ST3Gal II expression was suppressed by RelB siRNA, indicating that RelB activated ST3Gal II transcription in the testosterone-induced demethylated promoter. Therefore, in hormone-sensitive prostate cancers, the production of GD1a may be regulated by androgen. This is the first report indicating that the expression of a sialyltransferase is transcriptionally regulated by androgen-dependent demethylation of the CpG sites in its gene promoter.", "link"=>"http://www.mendeley.com/research/androgenregulated-transcriptional-control-sialyltransferases-prostate-cancer-cells", "reader_count"=>20, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>6, "Student > Master"=>1, "Lecturer"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Researcher"=>8, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>6, "Student > Master"=>1, "Lecturer"=>1}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Mathematics"=>1, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>7, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>7}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Mathematics"=>{"Mathematics"=>1}}, "reader_count_by_country"=>{"United States"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/684985"], "description"=>"<p>(A) The acidic GSLs from the cancerous tissue samples from eight patients with prostate cancer, including six patients with advanced hormone-sensitive prostate cancer and two patients with castration-resistant prostate cancer were separated by the molecular size of the oligosaccharides using normal-phase HPLC. Samples from one patient (designated Case 1) were taken from both the prostate and bone metastases for evaluation. (B) The acidic GSLs in the primary cancerous tissue samples were separated by the molecular size of the oligosaccharides using HPLC. The quantity of GD1a is presented as a percentage of the total acidic GSLs with GD1a. (C) The acidic GSLs in cultured prostate cancer cells were separated by the molecular size of the oligosaccharides using HPLC. The assay was done in triplicate, and the means ± S.E. GD1a levels are shown as the ratio to the total acidic GSLs in the cell lines. The mean ± S.E. GD1a level was also presented as the ratio to the total acidic GSLs in the patients' samples (HS+CR) indicated in <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031234#pone-0031234-g001\" target=\"_blank\">Figure 1B</a>. (HS, hormone-sensitive; CR, castration-resistant; F, free glycan).</p>", "links"=>[], "tags"=>["analyses", "gangliosides", "cancerous", "samples", "prostate", "cancer"], "article_id"=>355467, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Koji Hatano", "Yasuhide Miyamoto", "Masaki Mori", "Keisuke Nimura", "Yasutomo Nakai", "Norio Nonomura", "Yasufumi Kaneda"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031234.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_results_of_the_analyses_of_gangliosides_in_cancerous_tissue_samples_from_human_prostate_cancer_patients_/355467", "title"=>"The results of the analyses of gangliosides in cancerous tissue samples from human prostate cancer patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-08 01:31:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/685429"], "description"=>"<p>(A) LNCap cells were transfected with either scrambled RNA or RelB siRNA and incubated for 120 h with or without 100 nM testosterone. Protein extracts were prepared using RIPA lysis buffer, and the RelB expression level of each sample was analyzed by a Western blot analysis. The expression relative to β-actin is shown in each lane after normalizing the values to the expression level of the scrambled RNA–transfected and testosterone-untreated cells. (B) LNCap cells were transfected with the either scrambled RNA or RelB siRNA and incubated for 120 h with or without 100 nM testosterone. The quantitative real-time PCR analyses for ST3Gal I and II were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of the scrambled RNA–transfected and testosterone-untreated cells. *P<0.05, **P<0.001.</p>", "links"=>[], "tags"=>["androgen-dependent", "st3gal", "ii", "lncap"], "article_id"=>355912, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Koji Hatano", "Yasuhide Miyamoto", "Masaki Mori", "Keisuke Nimura", "Yasutomo Nakai", "Norio Nonomura", "Yasufumi Kaneda"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031234.g006", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_RelB_is_required_for_the_androgen_dependent_regulation_of_ST3Gal_I_and_II_in_LNCap_cells_/355912", "title"=>"RelB is required for the androgen-dependent regulation of ST3Gal I and II in LNCap cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-08 01:38:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/685112"], "description"=>"<p>(A) LNCap, PC3, and PNT2 cells were treated with or without testosterone (0–1000 nM) for 120 h, by refeeding with fresh medium with or without testosterone at 72 h. The quantitative real-time PCR analyses of ST3Gal II mRNA were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. **P<0.001. (B) LNCap cells were treated with or without testosterone (0–100 nM) and simultaneously with or without 10 µM bicalutamide for 120 h, by refeeding with fresh medium with or without testosterone and/or bicalutamide at 72 h. The quantitative real-time PCR analyses for ST3Gal II were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. **P<0.001. (C) LNCap cells were incubated in charcoal-stripped serum (CSS) for 48 h and then treated with 100 nM testosterone for the indicated times. The quantitative real-time PCR analyses for ST3Gal II were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. *P<0.05, **P<0.001.</p>", "links"=>[], "tags"=>["st3gal", "ii", "lncap"], "article_id"=>355595, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Koji Hatano", "Yasuhide Miyamoto", "Masaki Mori", "Keisuke Nimura", "Yasutomo Nakai", "Norio Nonomura", "Yasufumi Kaneda"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031234.g002", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Androgen_dependent_regulation_of_ST3Gal_II_in_LNCap_cells_/355595", "title"=>"Androgen-dependent regulation of ST3Gal II in LNCap cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-08 01:33:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/349105", "https://ndownloader.figshare.com/files/349115", "https://ndownloader.figshare.com/files/349133", "https://ndownloader.figshare.com/files/349156", "https://ndownloader.figshare.com/files/349171", "https://ndownloader.figshare.com/files/349182", "https://ndownloader.figshare.com/files/349200"], "description"=>"<div><p>The expression of gangliosides is often associated with cancer progression. Sialyltransferases have received much attention in terms of their relationship with cancer because they modulate the expression of gangliosides. We previously demonstrated that GD1a production was high in castration-resistant prostate cancer cell lines, PC3 and DU145, mainly due to their high expression of β-galactoside α2,3-sialyltransferase (ST3Gal) II (not ST3Gal I), and the expression of both ST3Gals was regulated by NF-κB, mainly by RelB. We herein demonstrate that GD1a was produced in abundance in cancerous tissue samples from human patients with hormone-sensitive prostate cancers as well as castration-resistant prostate cancers. The expression of ST3Gal II was constitutively activated in castration-resistant prostate cancer cell lines, PC3 and DU145, because of the hypomethylation of CpG island in its promoter. However, in androgen-depleted LNCap cells, a hormone-sensitive prostate cancer cell line, the expression of ST3Gal II was silenced because of the hypermethylation of the promoter region. The expression of ST3Gal II in LNCap cells increased with testosterone treatment because of the demethylation of the CpG sites. This testosterone-dependent ST3Gal II expression was suppressed by RelB siRNA, indicating that RelB activated ST3Gal II transcription in the testosterone-induced demethylated promoter. Therefore, in hormone-sensitive prostate cancers, the production of GD1a may be regulated by androgen. This is the first report indicating that the expression of a sialyltransferase is transcriptionally regulated by androgen-dependent demethylation of the CpG sites in its gene promoter.</p> </div>", "links"=>[], "tags"=>["androgen-regulated", "transcriptional", "sialyltransferases", "prostate", "cancer", "cells"], "article_id"=>129036, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Koji Hatano", "Yasuhide Miyamoto", "Masaki Mori", "Keisuke Nimura", "Yasutomo Nakai", "Norio Nonomura", "Yasufumi Kaneda"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0031234.s001", "https://dx.doi.org/10.1371/journal.pone.0031234.s002", "https://dx.doi.org/10.1371/journal.pone.0031234.s003", "https://dx.doi.org/10.1371/journal.pone.0031234.s004", "https://dx.doi.org/10.1371/journal.pone.0031234.s005", "https://dx.doi.org/10.1371/journal.pone.0031234.s006", "https://dx.doi.org/10.1371/journal.pone.0031234.s007"], "stats"=>{"downloads"=>8, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Androgen_Regulated_Transcriptional_Control_of_Sialyltransferases_in_Prostate_Cancer_Cells/129036", "title"=>"Androgen-Regulated Transcriptional Control of Sialyltransferases in Prostate Cancer Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-02-08 02:30:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/685511"], "description"=>"<p>HS, Hormone-sensitive; CR, Castration-resistant.</p>", "links"=>[], "tags"=>["genetics and genomics", "diabetes and endocrinology", "physiology", "Computational biology", "oncology", "Biochemistry"], "article_id"=>355991, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Koji Hatano", "Yasuhide Miyamoto", "Masaki Mori", "Keisuke Nimura", "Yasutomo Nakai", "Norio Nonomura", "Yasufumi Kaneda"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031234.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Patient_characteristics_/355991", "title"=>"Patient characteristics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-02-08 01:39:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/685260"], "description"=>"<p>(A) The CpG island in the ST3Gal II p1 promoter and the location of the MSP primers. The vertical bars represent CpG sites and TSS represents the transcriptional start site. (B–D) The MSP analyses of the CpG island of ST3Gal II. DNA was isolated from LNCap cells treated with 5-azadC (0–50 µM) for 120 h (B), castration-resistant prostate cancer cell lines (PC3 and DU145) or LNCap cells treated with or without 100 nM testosterone for 120 h (C) or LNCap cells treated with or without 100 nM testosterone simultaneously with or without 10 µM bicalutamide for 120 h (D). Then, the DNA was treated with sodium bisulfite, and finally amplified with primers specific for the unmethylated (USP) or the methylated (MSP) form of the CpG island in the ST3Gal II promoter (M, methylated control; UA, unmethylated control A; UB, unmethylated control B). The MSP analyses were repeated 3 times with the same results, and a representative image is shown in the figures.</p>", "links"=>[], "tags"=>["dna", "methylation", "cpg", "st3gal", "ii", "promoter", "prostate", "cancer"], "article_id"=>355736, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Koji Hatano", "Yasuhide Miyamoto", "Masaki Mori", "Keisuke Nimura", "Yasutomo Nakai", "Norio Nonomura", "Yasufumi Kaneda"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031234.g004", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Control_of_DNA_methylation_at_the_CpG_island_in_the_ST3Gal_II_promoter_in_prostate_cancer_cells_/355736", "title"=>"Control of DNA methylation at the CpG island in the ST3Gal II promoter in prostate cancer cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-08 01:35:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/685188"], "description"=>"<p>(A) LNCap cells were treated with 5-aza-2′-deoxycytidine (5-azadC) (0–50 µM) for 120 h, by refeeding with fresh medium with or without 5-azadC at 72 h. The quantitative real-time PCR analyses for ST3Gal II were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. *P<0.05. (B) LNCap cells were treated with 5 µM trichostatin A (TSA) for 48 h. The quantitative real-time PCR analyses for ST3Gal II were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. *P<0.05.</p>", "links"=>[], "tags"=>["st3gal", "ii", "lncap"], "article_id"=>355673, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Koji Hatano", "Yasuhide Miyamoto", "Masaki Mori", "Keisuke Nimura", "Yasutomo Nakai", "Norio Nonomura", "Yasufumi Kaneda"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031234.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Epigenetic_regulation_of_ST3Gal_II_in_LNCap_cells_/355673", "title"=>"Epigenetic regulation of ST3Gal II in LNCap cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-08 01:34:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/685350"], "description"=>"<p>(A) LNCap cells were treated with or without testosterone (0–1000 nM) for 120 h, by refeeding with fresh medium with or without testosterone at 72 h. The quantitative real-time PCR analyses for ST3Gal I were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. **P<0.001. (B) LNCap cells were treated with or without testosterone (0–100 nM) and simultaneously with or without 10 µM bicalutamide for 120 h, by refeeding with fresh medium with or without testosterone and/or bicalutamide at 72 h. The quantitative real-time PCR analyses for ST3Gal I were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. **P<0.001. (C) LNCap cells were incubated in charcoal-stripped serum (CSS) for 48 h and then treated with 100 nM testosterone for the indicated times. The quantitative real-time PCR analyses for ST3Gal I were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. *P<0.05, **P<0.001. (D) LNCap cells were treated with 5-aza-2′-deoxycytidine (5-azadC) (0–50 µM) for 120 h, by refeeding with fresh medium with or without 5-azadC at 72 h. The quantitative real-time PCR analyses for ST3Gal I were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. *P<0.05. (E) LNCap cells were treated with 5 µM trichostatin A (TSA) for 48 h. The quantitative real-time PCR analyses for ST3Gal I were performed, and the expression levels are reported as the means ± S.E. (n = 3) of the fold difference in mRNA after normalizing the values to the expression level of untreated cells. **P<0.001.</p>", "links"=>[], "tags"=>["epigenetic", "st3gal", "lncap"], "article_id"=>355836, "categories"=>["Chemistry", "Biochemistry", "Physiology", "Cancer", "Biological Sciences", "Genetics"], "users"=>["Koji Hatano", "Yasuhide Miyamoto", "Masaki Mori", "Keisuke Nimura", "Yasutomo Nakai", "Norio Nonomura", "Yasufumi Kaneda"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031234.g005", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Androgen_dependent_and_epigenetic_regulation_of_ST3Gal_I_in_LNCap_cells_/355836", "title"=>"Androgen-dependent and epigenetic regulation of ST3Gal I in LNCap cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-08 01:37:16"}

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Relative Metric

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