OpenLB
Open Library of Bioscience
Advanced Search
Cancer research
Nov 01, 2008;68 (21): 8852-60.

Identification of Pbx1, a potential oncogene, as a Notch3 target gene in ovarian cancer.

Joon T Park, Ie-Ming Shih, Tian-Li Wang
Author Information
  1. Joon T Park: Department of Pathology, Pathobiology Graduate Program, Johns Hopkins Medical Institutions, Baltimore, Maryland 21231, USA.
PMID: 18974129 DOI: 10.1158/0008-5472.CAN-08-0517

Abstract

Notch3 gene amplification has recently been identified in ovarian cancer but the Notch3 effectors that are involved in the development of ovarian cancer remain elusive. In this study, we have identified Pbx1, a proto-oncogene in hematopoietic malignancy, as a Notch3 target gene. Pbx1 expression is transcriptionally regulated by Notch3 activation, and Notch3/CSL protein complex directly binds to the Pbx1 promoter segment harboring the CSL-binding sequence. The growth-inhibitory effect of gamma-secretase inhibitor could be partially reversed by ectopic Pbx1 expression. Furthermore, functional studies by Pbx1 short hairpin RNA knockdown show that Pbx1 is essential for cell proliferation and tumorigenicity. Taken together, the above findings indicate that Pbx1 is a direct Notch3-regulated gene that mediates the survival signal of Notch3 in ovarian cancer.

References

  1. Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15209-14 [PMID: 11742062]
  2. Cancer Res. 2008 Jul 15;68(14):5716-23 [PMID: 18632624]
  3. Dev Biol. 2002 Apr 15;244(2):226-42 [PMID: 11944933]
  4. EMBO Rep. 2002 Jul;3(7):688-94 [PMID: 12101103]
  5. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16156-61 [PMID: 12461184]
  6. Dev Biol. 2003 Feb 15;254(2):262-76 [PMID: 12591246]
  7. Cancer Res. 2003 Jul 15;63(14):4144-9 [PMID: 12874019]
  8. Genes Dev. 2003 Aug 15;17(16):2060-72 [PMID: 12923056]
  9. Mol Cell. 2004 May 21;14(4):465-77 [PMID: 15149596]
  10. Science. 2004 Oct 8;306(5694):269-71 [PMID: 15472075]
  11. Cell. 1990 Feb 23;60(4):535-45 [PMID: 1967982]
  12. Cell. 1990 Feb 23;60(4):547-55 [PMID: 1967983]
  13. Genes Dev. 1991 Mar;5(3):358-68 [PMID: 1672117]
  14. Oncogene. 2000 Feb 3;19(5):608-16 [PMID: 10698505]
  15. J Natl Cancer Inst. 2000 Aug 16;92(16):1355-7 [PMID: 10944559]
  16. Blood. 2001 Aug 1;98(3):618-26 [PMID: 11468159]
  17. Cell. 1991 Aug 23;66(4):649-61 [PMID: 1831692]
  18. Mol Cell Biol. 2001 Sep;21(17):5925-34 [PMID: 11486031]
  19. Development. 2001 Sep;128(18):3543-57 [PMID: 11566859]
  20. Cell. 1994 Dec 30;79(7):1187-98 [PMID: 8001154]
  21. Nature. 1995 Sep 28;377(6547):355-8 [PMID: 7566092]
  22. Trends Genet. 1996 Jul;12(7):258-62 [PMID: 8763497]
  23. Cell. 1996 Nov 1;87(3):483-92 [PMID: 8898201]
  24. Mol Cell Biol. 1999 Jul;19(7):5134-42 [PMID: 10373562]
  25. Nature. 2004 Nov 18;432(7015):324-31 [PMID: 15549094]
  26. Nat Methods. 2004 Nov;1(2):109-11 [PMID: 15782172]
  27. Nat Med. 2005 May;11(5):531-7 [PMID: 15821746]
  28. Nature. 2005 Jun 16;435(7044):959-63 [PMID: 15959515]
  29. Nat Immunol. 2005 Jul;6(7):680-8 [PMID: 15991363]
  30. Oncogene. 2006 Jan 19;25(3):487-91 [PMID: 16186803]
  31. Blood. 2006 Apr 15;107(8):3313-20 [PMID: 16368887]
  32. Cancer Res. 2006 Jun 15;66(12):6312-8 [PMID: 16778208]
  33. Nature. 2006 Jul 6;442(7098):86-90 [PMID: 16728976]
  34. Genes Dev. 2006 Aug 1;20(15):2096-109 [PMID: 16847353]
  35. Oncogene. 2007 Jan 18;26(3):339-48 [PMID: 16862184]
  36. Chem Biol. 2007 Feb;14(2):209-19 [PMID: 17317574]
  37. Cancer Res. 2007 Mar 1;67(5):1879-82 [PMID: 17332312]
  38. Blood. 2007 May 15;109(10):4191-9 [PMID: 17244677]
  39. J Exp Med. 2007 Aug 6;204(8):1813-24 [PMID: 17646409]
  40. Proc Natl Acad Sci U S A. 2007 Oct 23;104(43):17093-8 [PMID: 17942676]
  41. Genes Dev. 2007 Nov 1;21(21):2762-74 [PMID: 17942707]
  42. Genes Dev. 2007 Nov 15;21(22):2845-9 [PMID: 18006680]
  43. Science. 2007 Nov 16;318(5853):1108-13 [PMID: 17932254]
  44. Nat Genet. 2002 Apr;30(4):430-5 [PMID: 11912494]

Grants

  1. CA103937/NCI NIH HHS
  2. R01 CA129080-01A1/NCI NIH HHS
  3. P50 CA098252/NCI NIH HHS
  4. R01 CA103937-05/NCI NIH HHS
  5. CA129080/NCI NIH HHS
  6. P50CA098252/NCI NIH HHS
  7. R01 CA129080/NCI NIH HHS
  8. R01 CA103937/NCI NIH HHS

MeSH Term

Base Sequence
Blotting, Western
Chromatin Immunoprecipitation
DNA Primers
DNA-Binding Proteins
Electrophoretic Mobility Shift Assay
Female
Humans
Oncogenes
Ovarian Neoplasms
Polymerase Chain Reaction
Pre-B-Cell Leukemia Transcription Factor 1
Proto-Oncogene Mas
Proto-Oncogene Proteins
Receptor, Notch3
Receptors, Notch
Signal Transduction

Chemicals

DNA Primers
DNA-Binding Proteins
MAS1 protein, human
NOTCH3 protein, human
Pre-B-Cell Leukemia Transcription Factor 1
Proto-Oncogene Mas
Proto-Oncogene Proteins
Receptor, Notch3
Receptors, Notch
PBX1 protein, human
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't
Article has an altmetric score of 6

Word Cloud

Created with Highcharts 10.0.0Pbx1Notch3geneovariancanceridentifiedtargetexpressionamplificationrecentlyeffectorsinvolveddevelopmentremainelusivestudyproto-oncogenehematopoieticmalignancytranscriptionallyregulatedactivationNotch3/CSLproteincomplexdirectlybindspromotersegmentharboringCSL-bindingsequencegrowth-inhibitoryeffectgamma-secretaseinhibitorpartiallyreversedectopicFurthermorefunctionalstudiesshorthairpinRNAknockdownshowessentialcellproliferationtumorigenicityTakentogetherfindingsindicatedirectNotch3-regulatedmediatessurvivalsignalIdentificationpotentialoncogene

Similar Articles

Cited By