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PMID: 16959035 Published · epublish English Journal Article Research Support, Non-U.S. Gov't Validation Study

Identification of genes regulated by Wnt/beta-catenin pathway and involved in apoptosis via microarray analysis.

BMC cancer ·Vol. 6 ·2006-09-07 ·Pages 221

Huang M, Wang Y, Sun D, Zhu H, Yin Y, Zhang W, Yang S, Quan L, Bai J, Wang S, Chen Q, Li S, Xu N

Abstract

Wnt/beta-catenin pathway has critical roles in development and oncogenesis. Although significant progress has been made in understanding the downstream signaling cascade of this pathway, little is known regarding Wnt/beta-catenin pathway modification of the cellular apoptosis. To identify potential genes regulated by Wnt/beta-catenin pathway and involved in apoptosis, we used a stably integrated, inducible RNA interference (RNAi) vector to specific inhibit the expression and the transcriptional activity of beta-catenin in HeLa cells. Meanwhile, we designed an oligonucleotide microarray covering 1384 apoptosis-related genes. Using oligonucleotide microarrays, a series of differential expression of genes was identified and further confirmed by RT-PCR. Stably integrated inducible RNAi vector could effectively suppress beta-catenin expression and the transcriptional activity of beta-catenin/TCF. Meanwhile, depletion of beta-catenin in this manner made the cells more sensitive to apoptosis. 130 genes involved in some important cell-apoptotic pathways, such as PTEN-PI3K-AKT pathway, NF-kappaB pathway and p53 pathway, showed significant alteration in their expression level after the knockdown of beta-catenin. Coupling RNAi knockdown with microarray and RT-PCR analyses proves to be a versatile strategy for identifying genes regulated by Wnt/beta-catenin pathway and for a better understanding the role of this pathway in apoptosis. Some of the identified beta-catenin/TCF directed or indirected target genes may represent excellent targets to limit tumor growth.

MeSH Terms
Apoptosis/genetics Cluster Analysis Down-Regulation HeLa Cells Humans Oligonucleotide Array Sequence Analysis/methods RNA Interference/physiology Signal Transduction/genetics T Cell Transcription Factor 1/metabolism Transcription, Genetic Transfection/methods Wnt Proteins/metabolism,physiology beta Catenin/metabolism,physiology
Chemicals
T Cell Transcription Factor 1 Wnt Proteins beta Catenin
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Huang Moli
Center of Bioinformatics, National Laboratory of Genetic Engineering and Protein Engineering, College of Life Sciences, Peking University, Beijing, PR China. huangml@mail.cbi.pku.edu.cn
Wang Yihua
Sun Daochun
Zhu Hongxia
Yin Yanbing
Zhang Wei
Yang Shangbin
Quan Lanping
Bai Jinfeng
Wang Shengqi
Chen Quan
Li Songgang
Xu Ningzhi
References (57)
57 references, click to expand
  1. An anti-Wnt-2 monoclonal antibody induces apoptosis in malignant melanoma cells and inhibits tumor growth.
    Cancer Res. 2004 Aug 1;64(15):5385-9 PMID: 15289346
  2. The death effector domain protein family: regulators of cellular homeostasis.
    Nat Immunol. 2003 May;4(5):404-9 PMID: 12719729
  3. WNT and beta-catenin signalling: diseases and therapies.
    Nat Rev Genet. 2004 Sep;5(9):691-701 PMID: 15372092
  4. Unlocking the potential of the human genome with RNA interference.
    Nature. 2004 Sep 16;431(7006):371-8 PMID: 15372045
  5. Two cellular proteins that bind to wild-type but not mutant p53.
    Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):6098-102 PMID: 8016121
  6. Stimulation of p53-mediated transcriptional activation by the p53-binding proteins, 53BP1 and 53BP2.
    J Biol Chem. 1998 Oct 2;273(40):26061-8 PMID: 9748285
  7. Structure-function analysis of an evolutionary conserved protein, DAP3, which mediates TNF-alpha- and Fas-induced cell death.
    EMBO J. 1999 Jan 15;18(2):353-62 PMID: 9889192
  8. Expression of CD44 in Apc and Tcf mutant mice implies regulation by the WNT pathway.
    Am J Pathol. 1999 Feb;154(2):515-23 PMID: 10027409
  9. Transcriptional activation of cyclooxygenase-2 in Wnt-1-transformed mouse mammary epithelial cells.
    Cancer Res. 1999 Apr 1;59(7):1572-7 PMID: 10197631
  10. The metalloproteinase matrilysin is a target of beta-catenin transactivation in intestinal tumors.
    Oncogene. 1999 May 6;18(18):2883-91 PMID: 10362259
  11. The TAK1-NLK-MAPK-related pathway antagonizes signalling between beta-catenin and transcription factor TCF.
    Nature. 1999 Jun 24;399(6738):798-802 PMID: 10391247
  12. beta-catenin regulates the expression of the matrix metalloproteinase-7 in human colorectal cancer.
    Am J Pathol. 1999 Oct;155(4):1033-8 PMID: 10514384
  13. Inhibition of Wnt signaling downregulates Akt activity and induces chemosensitivity in PTEN-mutated prostate cancer cells.
    Prostate. 2005 Jan 1;62(1):61-8 PMID: 15389810
  14. Blockade of Wnt-1 signaling induces apoptosis in human colorectal cancer cells containing downstream mutations.
    Oncogene. 2005 Apr 21;24(18):3054-8 PMID: 15735684
  15. Antisense Tcf inhibits the neoplastic growth of liver cancer cells.
    J Cancer Res Clin Oncol. 2004 Nov;130(11):671-8 PMID: 15221470
  16. Efficacy of Wnt-1 monoclonal antibody in sarcoma cells.
    BMC Cancer. 2005;5:53 PMID: 15913453
  17. Inhibition of Wnt16 in human acute lymphoblastoid leukemia cells containing the t(1;19) translocation induces apoptosis.
    Oncogene. 2005 Aug 11;24(34):5396-400 PMID: 16007226
  18. IKK/NF-kappaB signaling: balancing life and death--a new approach to cancer therapy.
    J Clin Invest. 2005 Oct;115(10):2625-32 PMID: 16200195
  19. Overexpression of EB1 in human esophageal squamous cell carcinoma (ESCC) may promote cellular growth by activating beta-catenin/TCF pathway.
    Oncogene. 2005 Oct 6;24(44):6637-45 PMID: 16007168
  20. The Wnt antagonist secreted frizzled-related protein-1 controls osteoblast and osteocyte apoptosis.
    J Cell Biochem. 2005 Dec 15;96(6):1212-30 PMID: 16149051
  21. Wnt proteins prevent apoptosis of both uncommitted osteoblast progenitors and differentiated osteoblasts by beta-catenin-dependent and -independent signaling cascades involving Src/ERK and phosphatidylinositol 3-kinase/AKT.
    J Biol Chem. 2005 Dec 16;280(50):41342-51 PMID: 16251184
  22. Beta-catenin-related anomalies in apoptosis-resistant and hormone-refractory prostate cancer cells.
    Clin Cancer Res. 2003 May;9(5):1801-7 PMID: 12738737
  23. Specific inhibition of gene expression using a stably integrated, inducible small-interfering-RNA vector.
    EMBO Rep. 2003 Jun;4(6):609-15 PMID: 12776180
  24. Caught up in a Wnt storm: Wnt signaling in cancer.
    Biochim Biophys Acta. 2003 Jun 5;1653(1):1-24 PMID: 12781368
  25. To be, or not to be: NF-kappaB is the answer--role of Rel/NF-kappaB in the regulation of apoptosis.
    Oncogene. 2003 Dec 8;22(56):8961-82 PMID: 14663476
  26. Beta-catenin is dispensable for hematopoiesis and lymphopoiesis.
    J Exp Med. 2004 Jan 19;199(2):221-9 PMID: 14718516
  27. Down-regulation of beta catenin inhibits the growth of esophageal carcinoma cells.
    J Thorac Cardiovasc Surg. 2004 Jan;127(1):92-8 PMID: 14752418
  28. A monoclonal antibody against Wnt-1 induces apoptosis in human cancer cells.
    Neoplasia. 2004 Jan-Feb;6(1):7-14 PMID: 15068666
  29. Improving the efficiency of RNA interference in mammals.
    Nat Rev Genet. 2004 May;5(5):355-65 PMID: 15143318
  30. RNA interference.
    BMJ. 2004 May 22;328(7450):1245-8 PMID: 15155505
  31. Wnt-7a causes loss of differentiated phenotype and inhibits apoptosis of articular chondrocytes via different mechanisms.
    J Biol Chem. 2004 Jun 18;279(25):26597-604 PMID: 15082716
  32. Ginsenoside Rg1-induced alterations in gene expression in TNF-alpha stimulated endothelial cells.
    Chin Med J (Engl). 2004 Jun;117(6):871-6 PMID: 15198890
  33. A P53 target gene, PIG11, contributes to chemosensitivity of cells to arsenic trioxide.
    FEBS Lett. 2004 Jul 2;569(1-3):94-8 PMID: 15225615
  34. Positive inter-regulation between beta-catenin/T cell factor-4 signaling and endothelin-1 signaling potentiates proliferation and survival of prostate cancer cells.
    Mol Pharmacol. 2006 Feb;69(2):520-31 PMID: 16291872
  35. Wnt/beta-catenin signaling inhibits death receptor-mediated apoptosis and promotes invasive growth of HNSCC.
    Cell Signal. 2006 May;18(5):679-87 PMID: 16084063
  36. Pathways of apoptotic and non-apoptotic death in tumour cells.
    Nat Rev Cancer. 2004 Aug;4(8):592-603 PMID: 15286739
  37. The PTEN tumor suppressor protein: an antagonist of phosphoinositide 3-kinase signaling.
    Biochim Biophys Acta. 2000 Feb 14;1470(1):M21-35 PMID: 10656987
  38. Wnt signaling in oncogenesis and embryogenesis--a look outside the nucleus.
    Science. 2000 Mar 3;287(5458):1606-9 PMID: 10733430
  39. Wnt-1 dependent activation of the survival factor NF-kappaB in PC12 cells.
    J Neurosci Res. 2000 Jul 1;61(1):21-32 PMID: 10861796
  40. Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis.
    J Clin Invest. 2000 Aug;106(4):533-9 PMID: 10953028
  41. Wnt-1 signaling inhibits apoptosis by activating beta-catenin/T cell factor-mediated transcription.
    J Cell Biol. 2001 Jan 8;152(1):87-96 PMID: 11149923
  42. The Hedgehog and Wnt signalling pathways in cancer.
    Nature. 2001 May 17;411(6835):349-54 PMID: 11357142
  43. The beta-catenin--TCF-1 pathway ensures CD4(+)CD8(+) thymocyte survival.
    Nat Immunol. 2001 Aug;2(8):691-7 PMID: 11477404
  44. Navigating gene expression using microarrays--a technology review.
    Nat Cell Biol. 2001 Aug;3(8):E190-5 PMID: 11483980
  45. Regulation of vascular endothelial growth factor by the Wnt and K-ras pathways in colonic neoplasia.
    Cancer Res. 2001 Aug 15;61(16):6050-4 PMID: 11507052
  46. New aspects of Wnt signaling pathways in higher vertebrates.
    Curr Opin Genet Dev. 2001 Oct;11(5):547-53 PMID: 11532397
  47. Id2 is a target of the beta-catenin/T cell factor pathway in colon carcinoma.
    J Biol Chem. 2001 Nov 30;276(48):45113-9 PMID: 11572874
  48. Nuclear translocation of PDCD5 (TFAR19): an early signal for apoptosis?
    FEBS Lett. 2001 Dec 7;509(2):191-6 PMID: 11741587
  49. Wnt/beta-catenin signaling suppresses apoptosis in low serum medium and induces morphologic change in rodent fibroblasts.
    Int J Cancer. 2002 Jun 10;99(5):681-8 PMID: 12115501
  50. Live or let die: the cell's response to p53.
    Nat Rev Cancer. 2002 Aug;2(8):594-604 PMID: 12154352
  51. PTEN overexpression suppresses proliferation and differentiation and enhances apoptosis of the mouse mammary epithelium.
    J Clin Invest. 2002 Sep;110(6):815-25 PMID: 12235113
  52. Wnt signaling protects 3T3-L1 preadipocytes from apoptosis through induction of insulin-like growth factors.
    J Biol Chem. 2002 Oct 11;277(41):38239-44 PMID: 12154096
  53. Beta-catenin antisense studies in embryonic liver cultures: role in proliferation, apoptosis, and lineage specification.
    Gastroenterology. 2003 Jan;124(1):202-16 PMID: 12512043
  54. beta-Catenin signaling: therapeutic strategies in oncology.
    Cancer Biol Ther. 2002 Nov-Dec;1(6):621-5 PMID: 12642683
  55. Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy.
    Leukemia. 2003 Mar;17(3):590-603 PMID: 12646949
  56. Senescence, apoptosis and therapy--cutting the lifelines of cancer.
    Nat Rev Cancer. 2003 Apr;3(4):286-95 PMID: 12671667
  57. Inhibition of Wnt-2-mediated signaling induces programmed cell death in non-small-cell lung cancer cells.
    Oncogene. 2004 Aug 12;23(36):6170-4 PMID: 15208662
Article Info
Journal
BMC cancer
Abbr.
BMC Cancer
ISSN
1471-2407
DOI
10.1186/1471-2407-6-221
Email
huangml@mail.cbi.pku.edu.cn
Published
2006-09-07
Epub
2006-00-07
Pages
221
Language
English
Region
England
NLM ID
100967800
PMCID
PMC1574340
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-2407-6-221 PMC Full Text View journal details
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