Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model

Handle URI:
http://hdl.handle.net/10754/325270
Title:
Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model
Authors:
Essack, Magbubah ( 0000-0003-2709-5356 ) ; MacPherson, Cameron Ross; Schmeier, Sebastian; Bajic, Vladimir B. ( 0000-0001-5435-4750 )
Abstract:
Background: Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.Results: Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.Conclusion: To the best of our knowledge our study is the first to use a cancer disease model as the framework to identify hormone responsive genes. Although we used ESCC as the disease model and estrogen as the hormone, the methodology can be extended analogously to other diseases as the model and other hormones. We believe that our results provide useful information for those interested in genes responsive to hormones and in the design of hormone-based therapies. 2012 Essack et al.; licensee BioMed Central Ltd.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Essack M, MacPherson C, Schmeier S, Bajic VB (2012) Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model. BMC Systems Biology 6: 135. doi:10.1186/1752-0509-6-135.
Publisher:
Springer Nature
Journal:
BMC Systems Biology
Issue Date:
26-Oct-2012
DOI:
10.1186/1752-0509-6-135
PubMed ID:
23101584
PubMed Central ID:
PMC3495646
Type:
Article
ISSN:
17520509
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorEssack, Magbubahen
dc.contributor.authorMacPherson, Cameron Rossen
dc.contributor.authorSchmeier, Sebastianen
dc.contributor.authorBajic, Vladimir B.en
dc.date.accessioned2014-08-27T09:43:53Z-
dc.date.available2014-08-27T09:43:53Z-
dc.date.issued2012-10-26en
dc.identifier.citationEssack M, MacPherson C, Schmeier S, Bajic VB (2012) Identification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a model. BMC Systems Biology 6: 135. doi:10.1186/1752-0509-6-135.en
dc.identifier.issn17520509en
dc.identifier.pmid23101584en
dc.identifier.doi10.1186/1752-0509-6-135en
dc.identifier.urihttp://hdl.handle.net/10754/325270en
dc.description.abstractBackground: Estrogen therapy has positively impact the treatment of several cancers, such as prostate, lung and breast cancers. Moreover, several groups have reported the importance of estrogen induced gene regulation in esophageal cancer (EC). This suggests that there could be a potential for estrogen therapy for EC. The efficient design of estrogen therapies requires as complete as possible list of genes responsive to estrogen. Our study develops a systems biology methodology using esophageal squamous cell carcinoma (ESCC) as a model to identify estrogen responsive genes. These genes, on the other hand, could be affected by estrogen therapy in ESCC.Results: Based on different sources of information we identified 418 genes implicated in ESCC. Putative estrogen responsive elements (EREs) mapped to the promoter region of the ESCC genes were used to initially identify candidate estrogen responsive genes. EREs mapped to the promoter sequence of 30.62% (128/418) of ESCC genes of which 43.75% (56/128) are known to be estrogen responsive, while 56.25% (72/128) are new candidate estrogen responsive genes. EREs did not map to 290 ESCC genes. Of these 290 genes, 50.34% (146/290) are known to be estrogen responsive. By analyzing transcription factor binding sites (TFBSs) in the promoters of the 202 (56+146) known estrogen responsive ESCC genes under study, we found that their regulatory potential may be characterized by 44 significantly over-represented co-localized TFBSs (cTFBSs). We were able to map these cTFBSs to promoters of 32 of the 72 new candidate estrogen responsive ESCC genes, thereby increasing confidence that these 32 ESCC genes are responsive to estrogen since their promoters contain both: a/mapped EREs, and b/at least four cTFBSs characteristic of ESCC genes that are responsive to estrogen. Recent publications confirm that 47% (15/32) of these 32 predicted genes are indeed responsive to estrogen.Conclusion: To the best of our knowledge our study is the first to use a cancer disease model as the framework to identify hormone responsive genes. Although we used ESCC as the disease model and estrogen as the hormone, the methodology can be extended analogously to other diseases as the model and other hormones. We believe that our results provide useful information for those interested in genes responsive to hormones and in the design of hormone-based therapies. 2012 Essack et al.; licensee BioMed Central Ltd.en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.subjectestrogenen
dc.subjecttranscription factoren
dc.subjectbinding siteen
dc.subjectDNA responsive elementen
dc.subjectdrug effecten
dc.subjectesophagus tumoren
dc.subjectgene expression regulationen
dc.subjectgenetic transcriptionen
dc.subjectgeneticsen
dc.subjectmetabolismen
dc.subjectmethodologyen
dc.subjectprotein transporten
dc.subjectsquamous cell carcinomaen
dc.subjectsystems biologyen
dc.subjectBinding Sitesen
dc.subjectCarcinoma, Squamous Cellen
dc.subjectEsophageal Neoplasmsen
dc.subjectEstrogensen
dc.subjectGene Expression Regulation, Neoplasticen
dc.subjectProtein Transporten
dc.subjectResponse Elementsen
dc.subjectSystems Biologyen
dc.subjectTranscription Factorsen
dc.subjectTranscription, Geneticen
dc.titleIdentification of estrogen responsive genes using esophageal squamous cell carcinoma (ESCC) as a modelen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalBMC Systems Biologyen
dc.identifier.pmcidPMC3495646en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionUnidad Académica de Sistemas Arrecifales (Puerto Morelos), Instituto de Ciencias Del Mar y Limnología, Universidad Nacional Autõnoma de México, Puerto Morelos, QR 77580, Mexicoen
dc.contributor.institutionSchool of Natural Sciences, University of California Merced, 5200 North Lake Road, Merced, CA 95343, United Statesen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorEssack, Magbubahen
kaust.authorMacPherson, Cameron R.en
kaust.authorSchmeier, Sebastianen
kaust.authorBajic, Vladimir B.en

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in KAUST are protected by copyright, with all rights reserved, unless otherwise indicated.