Article: The role of Pea3 group transcription factors in esophageal squamous cell carcinoma

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TitleThe role of Pea3 group transcription factors in esophageal squamous cell carcinoma
AuthorsYuen, HF2
McCrudden, CM2
Chan, KK2
Chan, YP1
Wong, MLY1
Chan, KYK1
Khoo, US1
Law, S1
Srivastava, G1
Lappin, TR2
Chan, KW1
ElTanani, M1 2
KeywordsApoptosis
Cancer growth
Cancer inhibition
Cancer invasion
Cancer resistance
Issue Date2011
PublisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
CitationAmerican Journal Of Pathology, 2011, v. 179 n. 2, p. 992-1003 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ajpath.2011.04.004
AbstractThe transcription factors Pea3, Erm, and Er81 can promote cancer initiation and progression in various types of solid tumors. However, their role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we found that the expression levels of Pea3 and Erm, but not that of Er81, were significantly higher in ESCC compared with nontumor esophageal epithelium. A high level of Pea3 expression was significantly correlated with a shorter overall survival in a cohort of 81 patients with ESCC and the subgroup with N1 stage tumor (Wilcoxon-Gehan test, P = 0.016 and P = 0.001, respectively). Pea3 was overexpressed in seven ESCC cell lines compared with two immortalized esophageal cell lines. Pea3 knockdown reduced cell proliferation and suppressed nonadherent growth, migration, and invasion in ESCC cells in vitro. In addition, Pea3 knockdown in ESCC cells resulted in a down-regulation of phospho-Akt and matrix metalloproteinase 13, whereas a significant positive correlation in the expression levels was observed between Pea3 and phospho-Akt (r = 0.281, P < 0.013) and between Pea3 and matrix metalloproteinase 13 in the human specimens (r = 0.462, P < 0.001). Moreover, Pea3 modulated the sensitivity of EC109 cells to doxorubicin, probably via reduced activity of the phosphatidylinositol 3-kinaseAktmammalian target of Rapamycin complex 1 pathway on Pea3 knockdown. In conclusion, our results suggest that Pea3 plays an important role in the progression of ESCC. © 2011 American Society for Investigative Pathology.
ISSN0002-9440
2011 Impact Factor: 4.89
2011 SCImago Journal Rankings: 0.697
DOIhttp://dx.doi.org/10.1016/j.ajpath.2011.04.004
ISI Accession Number IDWOS:000298307200043
Funding AgencyGrant Number
Cancer Research UK
Funding Information:

Supported by a postdoctoral fellowship from Cancer Research UK (H.-F.Y.).

PubMed Central IDPMC3157177
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorYuen, HF
dc.contributor.authorMcCrudden, CM
dc.contributor.authorChan, KK
dc.contributor.authorChan, YP
dc.contributor.authorWong, MLY
dc.contributor.authorChan, KYK
dc.contributor.authorKhoo, US
dc.contributor.authorLaw, S
dc.contributor.authorSrivastava, G
dc.contributor.authorLappin, TR
dc.contributor.authorChan, KW
dc.contributor.authorElTanani, M
dc.date.accessioned2011-08-26T14:29:51Z
dc.date.available2011-08-26T14:29:51Z
dc.date.issued2011
dc.description.abstractThe transcription factors Pea3, Erm, and Er81 can promote cancer initiation and progression in various types of solid tumors. However, their role in esophageal squamous cell carcinoma (ESCC) has not been elucidated. In this study, we found that the expression levels of Pea3 and Erm, but not that of Er81, were significantly higher in ESCC compared with nontumor esophageal epithelium. A high level of Pea3 expression was significantly correlated with a shorter overall survival in a cohort of 81 patients with ESCC and the subgroup with N1 stage tumor (Wilcoxon-Gehan test, P = 0.016 and P = 0.001, respectively). Pea3 was overexpressed in seven ESCC cell lines compared with two immortalized esophageal cell lines. Pea3 knockdown reduced cell proliferation and suppressed nonadherent growth, migration, and invasion in ESCC cells in vitro. In addition, Pea3 knockdown in ESCC cells resulted in a down-regulation of phospho-Akt and matrix metalloproteinase 13, whereas a significant positive correlation in the expression levels was observed between Pea3 and phospho-Akt (r = 0.281, P < 0.013) and between Pea3 and matrix metalloproteinase 13 in the human specimens (r = 0.462, P < 0.001). Moreover, Pea3 modulated the sensitivity of EC109 cells to doxorubicin, probably via reduced activity of the phosphatidylinositol 3-kinaseAktmammalian target of Rapamycin complex 1 pathway on Pea3 knockdown. In conclusion, our results suggest that Pea3 plays an important role in the progression of ESCC. © 2011 American Society for Investigative Pathology.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationAmerican Journal Of Pathology, 2011, v. 179 n. 2, p. 992-1003 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.ajpath.2011.04.004
dc.identifier.doihttp://dx.doi.org/10.1016/j.ajpath.2011.04.004
dc.identifier.epage1003
dc.identifier.hkuros191693
dc.identifier.isiWOS:000298307200043
Funding AgencyGrant Number
Cancer Research UK
Funding Information:

Supported by a postdoctoral fellowship from Cancer Research UK (H.-F.Y.).

dc.identifier.issn0002-9440
2011 Impact Factor: 4.89
2011 SCImago Journal Rankings: 0.697
dc.identifier.issue2
dc.identifier.openurl
dc.identifier.pmcidPMC3157177
dc.identifier.pmid21689625
dc.identifier.scopuseid_2-s2.0-80052485012
dc.identifier.spage992
dc.identifier.urihttp://hdl.handle.net/10722/137634
dc.identifier.volume179
dc.languageeng
dc.publisherAmerican Society for Investigative Pathology. The Journal's web site is located at http://www.amjpathol.org
dc.publisher.placeUnited States
dc.relation.ispartofAmerican Journal of Pathology
dc.relation.referencesReferences in Scopus
dc.subjectApoptosis
dc.subjectCancer growth
dc.subjectCancer inhibition
dc.subjectCancer invasion
dc.subjectCancer resistance
dc.titleThe role of Pea3 group transcription factors in esophageal squamous cell carcinoma
dc.typeArticle
Author Affiliations
  1. The University of Hong Kong
  2. Queen's University Belfast