Attenuated RORC Expression in the Presence of EMT Progression in Somatotroph Adenomas following Treatment with Somatostatin Analogs Is Associated with Poor Clinical Recovery
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{"title"=>"Attenuated RORC Expression in the Presence of EMT Progression in Somatotroph Adenomas following Treatment with Somatostatin Analogs Is Associated with Poor Clinical Recovery", "type"=>"journal", "authors"=>[{"first_name"=>"Tove", "last_name"=>"Lekva", "scopus_author_id"=>"22634574800"}, {"first_name"=>"Jens Petter", "last_name"=>"Berg", "scopus_author_id"=>"7401718171"}, {"first_name"=>"Ansgar", "last_name"=>"Heck", "scopus_author_id"=>"54684013300"}, {"first_name"=>"Stine", "last_name"=>"Lyngvi Fougner", "scopus_author_id"=>"55773460500"}, {"first_name"=>"Ole Kristoffer", "last_name"=>"Olstad", "scopus_author_id"=>"6701841882"}, {"first_name"=>"Geir", "last_name"=>"Ringstad", "scopus_author_id"=>"13907693200"}, {"first_name"=>"Jens", "last_name"=>"Bollerslev", "scopus_author_id"=>"7005151571"}, {"first_name"=>"Thor", "last_name"=>"Ueland", "scopus_author_id"=>"7007162539"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84879330115", "pui"=>"369184609", "doi"=>"10.1371/journal.pone.0066927", "sgr"=>"84879330115", "pmid"=>"23825587", "issn"=>"19326203"}, "id"=>"30d93260-796c-3301-9088-102722d504d3", "abstract"=>"Somatostatin analogs (SA) have been established as the first line medical treatment for acromegaly, but following long-term treatment, SA normalizes GH and IGF-I levels in only 40-60% of patients. The epithelial marker E-cadherin plays a crucial role in the epithelial mesenchymal transition (EMT) and is associated with a poor response to SA treatment. We hypothesized that the characterization of transcripts regulated by SA in somatotroph adenomas with high and low E-cadherin expression may identify signaling pathways and mediators that can explain the poor response to SA treatment. We performed a microarray analysis of sixteen adenomas with different levels of E-cadherin and SA treatment to identify regulated transcripts. Candidate transcripts were further explored in vivo in sixty-five adenomas, and interactions between SA treatment and EMT progression on mRNA expression profiles and associations with clinical recovery were assessed. Finally, the effects of SA treatment on adenoma cells in vitro from acromegalic patients were determined. Microarray analysis of selected adenomas with differential E-cadherin expression, as a marker of EMT progression, identified 172 genes that displayed differential expression that was dependent on SA treatment. The validation of selected candidates in the entire cohort identified 9 transcripts that showed an interaction between E-cadherin expression and SA treatment. Further analysis of the impact of these genes suggests that attenuated RORC expression in somatotroph adenomas is associated with increased tumor size and a blunted clinical response. Our study indicates that attenuated RORC may be involved in the poor clinical response to SA treatment in patients with acromegaly.", "link"=>"http://www.mendeley.com/research/attenuated-rorc-expression-presence-emt-progression-somatotroph-adenomas-following-treatment-somatos", "reader_count"=>13, "reader_count_by_academic_status"=>{"Researcher"=>2, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Researcher"=>2, "Student > Doctoral Student"=>2, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Biochemistry, Genetics and Molecular Biology"=>2, "Agricultural and Biological Sciences"=>5, "Medicine and Dentistry"=>5, "Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>2}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1100371"], "description"=>"a<p>Univariate, Pearson correlation: r (p = ). <b><sup>b</sup></b>Multivariate, Stepwise linear regression: B (SE), t = , p = . NA, not applicable.</p>", "links"=>[], "tags"=>["Computational biology", "Molecular genetics", "gene expression", "microarrays", "Molecular cell biology", "Signal transduction", "Signaling cascades", "statistics", "Biostatistics", "Statistical methods", "Clinical research design", "Endocrinology", "adrenal cortex", "Neuroendocrinology", "pituitary", "oncology", "Cancer treatment", "Endocrine therapy", "transcipts"], "article_id"=>730925, "categories"=>["Mathematics", "Medicine", "Biological Sciences"], "users"=>["Tove Lekva", "Jens Petter Berg", "Ansgar Heck", "Stine Lyngvi Fougner", "Ole Kristoffer Olstad", "Geir Ringstad", "Jens Bollerslev", "Thor Ueland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066927.t002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Associations_between_selected_transcipts_and_clinical_variables_/730925", "title"=>"Associations between selected transcipts and clinical variables.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-25 02:11:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1100370"], "description"=>"<p>Unless stated, data are given as median (25<sup>th</sup>, 75<sup>th</sup> percentile).</p>†<p>p<0.05 vs. Preoperative SA.</p>#<p>During acute octreotide test in patients not preoperatively treated with a somatostatin analog;</p>*<p>after median 6 months (range 2–32 months) preoperative SA treatment.</p>", "links"=>[], "tags"=>["Computational biology", "Molecular genetics", "gene expression", "microarrays", "Molecular cell biology", "Signal transduction", "Signaling cascades", "statistics", "Biostatistics", "Statistical methods", "Clinical research design", "Endocrinology", "adrenal cortex", "Neuroendocrinology", "pituitary", "oncology", "Cancer treatment", "Endocrine therapy"], "article_id"=>730924, "categories"=>["Mathematics", "Medicine", "Biological Sciences"], "users"=>["Tove Lekva", "Jens Petter Berg", "Ansgar Heck", "Stine Lyngvi Fougner", "Ole Kristoffer Olstad", "Geir Ringstad", "Jens Bollerslev", "Thor Ueland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066927.t001", "stats"=>{"downloads"=>9, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographics_of_the_study_population_/730924", "title"=>"Demographics of the study population.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-06-25 02:11:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1100361"], "description"=>"<p>(A) Overall study design. (B) Western blot of E-cadherin and GAPDH. Data for the E-cadherin protein ratio presented in the adenomas from E-cadherin gene expression tertile 1 and tertile 3. Correlation plot between E-cadherin protein and mRNA levels. (C) Gene expression profiles of differentially expressed genes in 16 adenomas selected from low and high tertiles of E-cadherin expression; 4 adenomas in each tertile were pretreated with SA. Gene expression levels for each adenoma are presented in horizontal rows with colors indicating upregulated (red) or downregulated (blue) genes. A total of 172 genes were differentially expressed in response to SA; 57 were downregulated and 1 was upregulated in tertile 1, while 93 were downregulated and 22 were upregulated in tertile 3 (mean fold change ≥2.0 and p<0.05). Each column represents a single gene. (D) A more detailed gene expression profile is presented for the 24 selected transcripts. The color intensity represents the degree of regulation; green indicates downregulation, while and red indicates upregulation. (E) Regulated SA transcripts presented. Transcripts were selected based on their known association with EMT or E-cadherin (*) or were chosen because of their strong regulation by the different levels of E-cadherin expression and by SA (†) (mean fold change ≥2.0 and p<0.01).</p>", "links"=>[], "tags"=>["Computational biology", "Molecular genetics", "gene expression", "microarrays", "Molecular cell biology", "Signal transduction", "Signaling cascades", "statistics", "Biostatistics", "Statistical methods", "Clinical research design", "Endocrinology", "adrenal cortex", "Neuroendocrinology", "pituitary", "oncology", "Cancer treatment", "Endocrine therapy"], "article_id"=>730915, "categories"=>["Mathematics", "Medicine", "Biological Sciences"], "users"=>["Tove Lekva", "Jens Petter Berg", "Ansgar Heck", "Stine Lyngvi Fougner", "Ole Kristoffer Olstad", "Geir Ringstad", "Jens Bollerslev", "Thor Ueland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066927.g001", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Study_designs_/730915", "title"=>"Study designs.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-25 02:11:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1100372", "https://ndownloader.figshare.com/files/1100373"], "description"=>"<div><p>Somatostatin analogs (SA) have been established as the first line medical treatment for acromegaly, but following long-term treatment, SA normalizes GH and IGF-I levels in only 40–60% of patients. The epithelial marker E-cadherin plays a crucial role in the epithelial mesenchymal transition (EMT) and is associated with a poor response to SA treatment. We hypothesized that the characterization of transcripts regulated by SA in somatotroph adenomas with high and low E-cadherin expression may identify signaling pathways and mediators that can explain the poor response to SA treatment. We performed a microarray analysis of sixteen adenomas with different levels of E-cadherin and SA treatment to identify regulated transcripts. Candidate transcripts were further explored <i>in vivo</i> in sixty-five adenomas, and interactions between SA treatment and EMT progression on mRNA expression profiles and associations with clinical recovery were assessed. Finally, the effects of SA treatment on adenoma cells <i>in vitro</i> from acromegalic patients were determined. Microarray analysis of selected adenomas with differential E-cadherin expression, as a marker of EMT progression, identified 172 genes that displayed differential expression that was dependent on SA treatment. The validation of selected candidates in the entire cohort identified 9 transcripts that showed an interaction between E-cadherin expression and SA treatment. Further analysis of the impact of these genes suggests that attenuated RORC expression in somatotroph adenomas is associated with increased tumor size and a blunted clinical response. Our study indicates that attenuated RORC may be involved in the poor clinical response to SA treatment in patients with acromegaly.</p></div>", "links"=>[], "tags"=>["Computational biology", "Molecular genetics", "gene expression", "microarrays", "Molecular cell biology", "Signal transduction", "Signaling cascades", "statistics", "Biostatistics", "Statistical methods", "Clinical research design", "Endocrinology", "adrenal cortex", "Neuroendocrinology", "pituitary", "oncology", "Cancer treatment", "Endocrine therapy", "rorc", "emt", "progression", "somatotroph", "adenomas", "somatostatin", "analogs"], "article_id"=>730926, "categories"=>["Mathematics", "Medicine", "Biological Sciences"], "users"=>["Tove Lekva", "Jens Petter Berg", "Ansgar Heck", "Stine Lyngvi Fougner", "Ole Kristoffer Olstad", "Geir Ringstad", "Jens Bollerslev", "Thor Ueland"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0066927.s001", "https://dx.doi.org/10.1371/journal.pone.0066927.s002"], "stats"=>{"downloads"=>0, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Attenuated_RORC_Expression_in_the_Presence_of_EMT_Progression_in_Somatotroph_Adenomas_following_Treatment_with_Somatostatin_Analogs_Is_Associated_with_Poor_Clinical_Recovery_/730926", "title"=>"Attenuated RORC Expression in the Presence of EMT Progression in Somatotroph Adenomas following Treatment with Somatostatin Analogs Is Associated with Poor Clinical Recovery", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-06-25 02:11:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1100369"], "description"=>"<p>Gene expression of (A) RORC following 6 and 24 h of treatment with octreotide (10<sup>−8</sup> M) in quadruplicate, normalized to β-actin and expressed as relative mRNA levels. There were two of the adenomas that had an E-cadherin mRNA expression level 300 times lower than the other three, in the adenoma tissue before any culturing. The results are from five independent experiments and presented as the mean ± SEM, * <i>p</i><0.05 indicating difference between untreated control and octreotide-treated cells normalized to untreated control at each time point.</p>", "links"=>[], "tags"=>["Computational biology", "Molecular genetics", "gene expression", "microarrays", "Molecular cell biology", "Signal transduction", "Signaling cascades", "statistics", "Biostatistics", "Statistical methods", "Clinical research design", "Endocrinology", "adrenal cortex", "Neuroendocrinology", "pituitary", "oncology", "Cancer treatment", "Endocrine therapy", "gh", "tumors", "acromegalic"], "article_id"=>730923, "categories"=>["Mathematics", "Medicine", "Biological Sciences"], "users"=>["Tove Lekva", "Jens Petter Berg", "Ansgar Heck", "Stine Lyngvi Fougner", "Ole Kristoffer Olstad", "Geir Ringstad", "Jens Bollerslev", "Thor Ueland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066927.g004", "stats"=>{"downloads"=>0, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Octreotide_treatment_of_human_pituitary_GH_tumors_from_acromegalic_patients_/730923", "title"=>"Octreotide treatment of human pituitary GH tumors from acromegalic patients.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-25 02:11:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1100368"], "description"=>"<p>Matrix scatter plots between <i>RORC</i> and the response to the acute SA test, tumor size, tumor size reduction and IGF-I reduction.</p>", "links"=>[], "tags"=>["Computational biology", "Molecular genetics", "gene expression", "microarrays", "Molecular cell biology", "Signal transduction", "Signaling cascades", "statistics", "Biostatistics", "Statistical methods", "Clinical research design", "Endocrinology", "adrenal cortex", "Neuroendocrinology", "pituitary", "oncology", "Cancer treatment", "Endocrine therapy", "acute", "sa", "igf-i"], "article_id"=>730922, "categories"=>["Mathematics", "Medicine", "Biological Sciences"], "users"=>["Tove Lekva", "Jens Petter Berg", "Ansgar Heck", "Stine Lyngvi Fougner", "Ole Kristoffer Olstad", "Geir Ringstad", "Jens Bollerslev", "Thor Ueland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066927.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Matrix_scatter_plots_between_RORC_and_the_response_to_the_acute_SA_test_tumor_size_tumor_size_reduction_and_IGF_I_reduction_/730922", "title"=>"Matrix scatter plots between <i>RORC</i> and the response to the acute SA test, tumor size, tumor size reduction and IGF-I reduction.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-25 02:11:20"}
  • {"files"=>["https://ndownloader.figshare.com/files/1100363"], "description"=>"<p>The transcripts of (A) RORC (B) ITGAV (C) CTTNBP2 (D) TIMP1 (E) DOK6 (F) MBNL3 (G) NOX4 (H) VLDLR and (I) KCNIP3 in 65 growth hormone-producing adenomas were selected based on the interaction between E-cadherin and SA (p<0.1, interaction tested with continuous E-cadherin, but presented as tertiles), quantified and distributed according to tertiles of E-cadherin mRNA expression (normalized to GAPDH mRNA levels and expressed as relative mRNA levels). The results are presented as the mean ± SEM and presented relative to tertile 1. P-values represent the interaction between E-cadherin and SA in the univariate analysis.</p>", "links"=>[], "tags"=>["Computational biology", "Molecular genetics", "gene expression", "microarrays", "Molecular cell biology", "Signal transduction", "Signaling cascades", "statistics", "Biostatistics", "Statistical methods", "Clinical research design", "Endocrinology", "adrenal cortex", "Neuroendocrinology", "pituitary", "oncology", "Cancer treatment", "Endocrine therapy", "rt-pcr", "transcripts", "somatotroph", "supported", "E-cadherin", "sa"], "article_id"=>730917, "categories"=>["Mathematics", "Medicine", "Biological Sciences"], "users"=>["Tove Lekva", "Jens Petter Berg", "Ansgar Heck", "Stine Lyngvi Fougner", "Ole Kristoffer Olstad", "Geir Ringstad", "Jens Bollerslev", "Thor Ueland"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0066927.g002", "stats"=>{"downloads"=>0, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Quantitative_real_time_RT_PCR_of_selected_gene_transcripts_in_somatotroph_adenomas_which_supported_an_interaction_between_E_cadherin_expression_levels_and_SA_treatment_/730917", "title"=>"Quantitative real time RT-PCR of selected gene transcripts in somatotroph adenomas, which supported an interaction between E-cadherin expression levels and SA treatment.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-06-25 02:11:20"}

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  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"1", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"6", "full-text"=>"5", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"4", "full-text"=>"5", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"9"}
  • {"unique-ip"=>"2", "full-text"=>"1", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"1", "cited-by"=>"0", "year"=>"2018", "month"=>"11"}
  • {"unique-ip"=>"7", "full-text"=>"6", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"3", "full-text"=>"2", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"4", "full-text"=>"3", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"9", "full-text"=>"12", "pdf"=>"2", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"2", "supp-data"=>"5", "cited-by"=>"0", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Anatomy", "average_usage"=>[248, 440, 562, 666, 765, 856, 944, 1028, 1112, 1198, 1282, 1362, 1430]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Biology and life sciences/Neuroscience", "average_usage"=>[261, 444, 554, 655, 748, 834, 923, 1004, 1089, 1170, 1244, 1315, 1380]}, {"subject_area"=>"/Medicine and health sciences", "average_usage"=>[264, 460, 584, 692, 794, 887, 978, 1067, 1154, 1241, 1328, 1408, 1474]}, {"subject_area"=>"/Medicine and health sciences/Anatomy", "average_usage"=>[248, 441, 564, 668, 769, 859, 948, 1034, 1117, 1202, 1290, 1368, 1437]}]}
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