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Conference Paper: Differential expression and functional impact of the alternatively spliced transcripts of Extracellular matrix protein 1 in esophageal squamous cell carcinoma

TitleDifferential expression and functional impact of the alternatively spliced transcripts of Extracellular matrix protein 1 in esophageal squamous cell carcinoma
Other TitlesDifferential expression and functional impact of the alternatively spliced transcripts of ECM1 in esophageal squamous cell carcinoma
Authors
Issue Date2016
PublisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/
Citation
The 107th Annual Meeting of American Association for Cancer Research (AACR 2016), New Orleans, LA., 16-20 April 2016. In Cancer Research, 2016, v. 76 n. 14 suppl., abstract no. 1158 How to Cite?
AbstractBACKGROUND: Esophageal squamous cell carcinoma (ESCC) has an especially high incidence in China, with five-year survival rates in Hong Kong being of ∼14%. An oligonucleotide microarray was utilized to identify differentially-expressed genes in ESCC using 31 pairs of matched normal/tumor samples from Hong Kong and Henan, China. Extracellular matrix protein 1 (ECM1) was among the top down-regulated genes, indicating a potential tumor-suppressive role. Public cDNA microarray data also shows significant down-regulation of ECM1 expression in ESCC. Interestingly, this gene has been extensively studied in breast cancer and thyroid cancer for its oncogenic role. There are three alternatively-spliced variants of ECM1. Therefore, this gene was selected for further variant expression and functional analysis in ESCC. RESULTS: RNA sequencing analysis of matched normal/ESCC samples showed that ECM1b (NM_022664) is the dominant expressed variant in esophagus, followed by ECM1a (NM_004425). In tumor samples, the expression of ECM1a is down-regulated and that of ECM1b is down-regulated or lost, as compared to normal counterparts. Expression of ECM1c (NM_001202858) is not detected in either normal or tumor samples. Quantitative PCR using variant-specific primer sets confirms the findings of microarray and RNA sequencing analyses. When re-expressed in ESCC cell lines after lentiviral transduction, ECM1b expression shows a trend of tumor suppression in the orthotopic ESCC mouse tumorigenicity model; ECM1a shows no tumor-suppressive effect in either. ECM1b expression also shows a metastasis inhibitory effect in a tail vein experimental metastasis model. Immunohistochemical staining shows E-cadherin up-regulation in orthotopic tumors re-expressing ECM1b. CONCLUSIONS: These results suggest differential roles of variants of ECM1 in ESCC. Unlike the cases in other types of cancer, both expression of ECM1a and ECM1b is down-regulated in ESCC compared to normal esophageal tissues. ECM1b represents the dominantly expressed variants in esophagus epithelium, and its expression is highly reduced in esophageal carcinoma. ECM1b plays a potential suppressive role in tumorigenesis and metastasis.
DescriptionConference Theme: Bayer to Present New Data on Advancing Oncology Portfolio
Session: Molecular and Cellular Biology, Genetics
This journal suppl. is Proceedings: AACR 107th Annual Meeting 2016
Persistent Identifierhttp://hdl.handle.net/10722/227563
ISSN
2015 Impact Factor: 8.556
2015 SCImago Journal Rankings: 5.372

 

DC FieldValueLanguage
dc.contributor.authorYu, VZ-
dc.contributor.authorKo, JMY-
dc.contributor.authorLaw, S-
dc.contributor.authorWang, LD-
dc.contributor.authorLung, ML-
dc.date.accessioned2016-07-18T09:11:29Z-
dc.date.available2016-07-18T09:11:29Z-
dc.date.issued2016-
dc.identifier.citationThe 107th Annual Meeting of American Association for Cancer Research (AACR 2016), New Orleans, LA., 16-20 April 2016. In Cancer Research, 2016, v. 76 n. 14 suppl., abstract no. 1158-
dc.identifier.issn0008-5472-
dc.identifier.urihttp://hdl.handle.net/10722/227563-
dc.descriptionConference Theme: Bayer to Present New Data on Advancing Oncology Portfolio-
dc.descriptionSession: Molecular and Cellular Biology, Genetics-
dc.descriptionThis journal suppl. is Proceedings: AACR 107th Annual Meeting 2016-
dc.description.abstractBACKGROUND: Esophageal squamous cell carcinoma (ESCC) has an especially high incidence in China, with five-year survival rates in Hong Kong being of ∼14%. An oligonucleotide microarray was utilized to identify differentially-expressed genes in ESCC using 31 pairs of matched normal/tumor samples from Hong Kong and Henan, China. Extracellular matrix protein 1 (ECM1) was among the top down-regulated genes, indicating a potential tumor-suppressive role. Public cDNA microarray data also shows significant down-regulation of ECM1 expression in ESCC. Interestingly, this gene has been extensively studied in breast cancer and thyroid cancer for its oncogenic role. There are three alternatively-spliced variants of ECM1. Therefore, this gene was selected for further variant expression and functional analysis in ESCC. RESULTS: RNA sequencing analysis of matched normal/ESCC samples showed that ECM1b (NM_022664) is the dominant expressed variant in esophagus, followed by ECM1a (NM_004425). In tumor samples, the expression of ECM1a is down-regulated and that of ECM1b is down-regulated or lost, as compared to normal counterparts. Expression of ECM1c (NM_001202858) is not detected in either normal or tumor samples. Quantitative PCR using variant-specific primer sets confirms the findings of microarray and RNA sequencing analyses. When re-expressed in ESCC cell lines after lentiviral transduction, ECM1b expression shows a trend of tumor suppression in the orthotopic ESCC mouse tumorigenicity model; ECM1a shows no tumor-suppressive effect in either. ECM1b expression also shows a metastasis inhibitory effect in a tail vein experimental metastasis model. Immunohistochemical staining shows E-cadherin up-regulation in orthotopic tumors re-expressing ECM1b. CONCLUSIONS: These results suggest differential roles of variants of ECM1 in ESCC. Unlike the cases in other types of cancer, both expression of ECM1a and ECM1b is down-regulated in ESCC compared to normal esophageal tissues. ECM1b represents the dominantly expressed variants in esophagus epithelium, and its expression is highly reduced in esophageal carcinoma. ECM1b plays a potential suppressive role in tumorigenesis and metastasis.-
dc.languageeng-
dc.publisherAmerican Association for Cancer Research. The Journal's web site is located at http://cancerres.aacrjournals.org/-
dc.relation.ispartofCancer Research-
dc.titleDifferential expression and functional impact of the alternatively spliced transcripts of Extracellular matrix protein 1 in esophageal squamous cell carcinoma-
dc.title.alternativeDifferential expression and functional impact of the alternatively spliced transcripts of ECM1 in esophageal squamous cell carcinoma-
dc.typeConference_Paper-
dc.identifier.emailYu, VZ: zvyu@hku.hk-
dc.identifier.emailKo, JMY: joko@hku.hk-
dc.identifier.emailLaw, S: slaw@hkucc.hku.hk-
dc.identifier.emailLung, ML: mlilung@hku.hk-
dc.identifier.authorityKo, JMY=rp02011-
dc.identifier.authorityLaw, S=rp00437-
dc.identifier.authorityLung, ML=rp00300-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1158/1538-7445.AM2016-1158-
dc.identifier.hkuros259653-
dc.identifier.volume76-
dc.identifier.issue14 suppl., abstract no. 1158-
dc.publisher.placeUnited States-

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