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Induction of ectopic Myc target gene JAG2 augments hypoxic growth and tumorigenesis in a human B-cell model.

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Title: Induction of ectopic Myc target gene JAG2 augments hypoxic growth and tumorigenesis in a human B-cell model.
Authors: Yustein, Jason T.1,2 yustein@bcm.edu, Yen-Chun Liu3, Ping Gao4, Chunfa Jie5, Le, Anne4, Vuica-Ross, Milena3, Wee Joo Chng6,7, Eberhart, Charles G.3, Bergsagel, P. Leif6, Dang, Chi V.3,4,8 cvdang@jhmi.edu
Source: Proceedings of the National Academy of Sciences of the United States of America. 2/23/2010, Vol. 107 Issue 8, p3534-3539. 6p. 2 Diagrams, 3 Graphs.
Subjects: Ectopic tissue, Carcinogenesis, B cells, Precancerous conditions, Hypoxemia
Abstract: Ectopic Myc expression plays a key role in human tumorigenesis, and Myc dose-dependent tumorigenesis has been well established in transgenic mice, but the Myc target genes that are dependent on Myc levels have not been well characterized. In this regard, we used the human P493-6 B cells, which have a preneoplastic state dependent on the Epstein-Barr viral EBNA2 protein and a neoplastic state with ectopic inducible Myc, to identify putative ectopic Myc target genes. Among the ectopic targets, JAG2 that encodes a Notch receptor ligand Jagged2, was directly induced by Myc. Inhibition of Notch signaling through RNAi targeting JAG2 or the γ-secretase Notch inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester (DAPT) preferentially inhibited the neoplastic state in vitro. Furthermore, P493-6 tumorigenesis was inhibited by DAPT in vivo. Ectopic expression of JAG2 did not enhance aerobic cell proliferation, but increased proliferation of hypoxic cells in vitro and significantly increased in vivo tumorigenesis. Furthermore, the expression of Jagged2 in P493-6 tumors often overlapped with regions of hypoxia. These observations suggest that Notch signaling downstream of Myc enables cells to adapt in the tumor hypoxic microenvironment. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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DbLabel: Engineering Source
An: 48439773
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
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  Data: Induction of ectopic Myc target gene JAG2 augments hypoxic growth and tumorigenesis in a human B-cell model.
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  Data: <searchLink fieldCode="AR" term="%22Yustein%2C+Jason+T%2E%22">Yustein, Jason T.</searchLink><relatesTo>1,2</relatesTo><i> yustein@bcm.edu</i><br /><searchLink fieldCode="AR" term="%22Yen-Chun+Liu%22">Yen-Chun Liu</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Ping+Gao%22">Ping Gao</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Chunfa+Jie%22">Chunfa Jie</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Le%2C+Anne%22">Le, Anne</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Vuica-Ross%2C+Milena%22">Vuica-Ross, Milena</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Wee+Joo+Chng%22">Wee Joo Chng</searchLink><relatesTo>6,7</relatesTo><br /><searchLink fieldCode="AR" term="%22Eberhart%2C+Charles+G%2E%22">Eberhart, Charles G.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Bergsagel%2C+P%2E+Leif%22">Bergsagel, P. Leif</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Dang%2C+Chi+V%2E%22">Dang, Chi V.</searchLink><relatesTo>3,4,8</relatesTo><i> cvdang@jhmi.edu</i>
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  Data: <searchLink fieldCode="JN" term="%22Proceedings+of+the+National+Academy+of+Sciences+of+the+United+States+of+America%22">Proceedings of the National Academy of Sciences of the United States of America</searchLink>. 2/23/2010, Vol. 107 Issue 8, p3534-3539. 6p. 2 Diagrams, 3 Graphs.
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  Data: <searchLink fieldCode="DE" term="%22Ectopic+tissue%22">Ectopic tissue</searchLink><br /><searchLink fieldCode="DE" term="%22Carcinogenesis%22">Carcinogenesis</searchLink><br /><searchLink fieldCode="DE" term="%22B+cells%22">B cells</searchLink><br /><searchLink fieldCode="DE" term="%22Precancerous+conditions%22">Precancerous conditions</searchLink><br /><searchLink fieldCode="DE" term="%22Hypoxemia%22">Hypoxemia</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Ectopic Myc expression plays a key role in human tumorigenesis, and Myc dose-dependent tumorigenesis has been well established in transgenic mice, but the Myc target genes that are dependent on Myc levels have not been well characterized. In this regard, we used the human P493-6 B cells, which have a preneoplastic state dependent on the Epstein-Barr viral EBNA2 protein and a neoplastic state with ectopic inducible Myc, to identify putative ectopic Myc target genes. Among the ectopic targets, JAG2 that encodes a Notch receptor ligand Jagged2, was directly induced by Myc. Inhibition of Notch signaling through RNAi targeting JAG2 or the γ-secretase Notch inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester (DAPT) preferentially inhibited the neoplastic state in vitro. Furthermore, P493-6 tumorigenesis was inhibited by DAPT in vivo. Ectopic expression of JAG2 did not enhance aerobic cell proliferation, but increased proliferation of hypoxic cells in vitro and significantly increased in vivo tumorigenesis. Furthermore, the expression of Jagged2 in P493-6 tumors often overlapped with regions of hypoxia. These observations suggest that Notch signaling downstream of Myc enables cells to adapt in the tumor hypoxic microenvironment. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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RecordInfo BibRecord:
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      – Type: doi
        Value: 10.1073/pnas.0901230107
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      – Code: eng
        Text: English
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        PageCount: 6
        StartPage: 3534
    Subjects:
      – SubjectFull: Ectopic tissue
        Type: general
      – SubjectFull: Carcinogenesis
        Type: general
      – SubjectFull: B cells
        Type: general
      – SubjectFull: Precancerous conditions
        Type: general
      – SubjectFull: Hypoxemia
        Type: general
    Titles:
      – TitleFull: Induction of ectopic Myc target gene JAG2 augments hypoxic growth and tumorigenesis in a human B-cell model.
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              Text: 2/23/2010
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              Y: 2010
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