Home LiteratureArticle Details
PMID: 16637074 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Protocadherin-PC promotes androgen-independent prostate cancer cell growth.

The Prostate ·Vol. 66 ·No. 10 ·2006-07-01 ·Pages 1100-13

Terry S, Queires L, Gil-Diez-de-Medina S, Chen MW, de la Taille A, Allory Y, Tran PL, Abbou CC, Buttyan R, Vacherot F

Abstract

Protocadherin-PC (PCDH-PC) expression is upregulated in apoptosis-resistant sublines of the LNCaP human prostate cancer (CaP) cell line. Here, we assess the role of PCDH-PC in CaP cells and its mRNA expression in human prostate tissues. LNCaP cells transfected with PCDH-PC were tested for their ability to grow in vitro and in vivo in androgen-deprived conditions. PCDH-PC mRNA expression was evaluated by semi-quantitative RT-PCR and by in situ hybridization. PCDH-PC expression induced Wnt signaling in CaP cells and permitted androgen-independent growth of hormone-sensitive CaP cells. Expression of PCDH-PC-homologous transcripts was low and restricted to some epithelial cells in normal tissue and to CaP cells in tumors. However, hormone-resistant CaP cells expressed significantly higher levels of PCDH-PC-related mRNA. Our findings suggest a novel mechanism for the progression of CaP involving expression of PCDH-PC. This novel protocadherin induces Wnt signaling, promotes malignant behavior and hormone-resistance of CaP cells.

MeSH Terms
Androgens/physiology Animals Apoptosis/physiology Cadherins/analysis,genetics,physiology Cell Line, Tumor Cell Proliferation Gene Expression Regulation, Neoplastic Humans Immunohistochemistry In Situ Hybridization Male Mice Mice, Nude Neoplasms, Hormone-Dependent/chemistry,genetics,pathology,physiopathology Prostate/chemistry Prostatic Neoplasms/chemistry,genetics,pathology,physiopathology Protocadherins RNA, Messenger/analysis,genetics Reverse Transcriptase Polymerase Chain Reaction Signal Transduction/physiology TCF Transcription Factors/physiology Wnt Proteins/genetics,physiology Xenograft Model Antitumor Assays
Chemicals
Androgens Cadherins PCDH11Y protein, human Protocadherins RNA, Messenger TCF Transcription Factors Wnt Proteins
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Terry Stephane
Department of Urology and Pathology of CHU Henri Mondor, INSERM E 03-37, Université Paris XII, Centre de Recherches Chirurgicales, Assistance Publique des Hôpitaux de Paris, Créteil, France.
Queires Luis
Gil-Diez-de-Medina Sixtina
Chen Min-Wei
de la Taille Alexandre
Allory Yves
Tran Phuong-Lan
Abbou Claude C
Buttyan Ralph
Vacherot Francis
References (55)
55 references, click to expand
  1. Cancer statistics, 1999.
    CA Cancer J Clin. 1999 Jan-Feb;49(1):8-31, 1 PMID: 10200775
  2. Neuropeptide-induced androgen independence in prostate cancer cells: roles of nonreceptor tyrosine kinases Etk/Bmx, Src, and focal adhesion kinase.
    Mol Cell Biol. 2001 Dec;21(24):8385-97 PMID: 11713275
  3. Wnt signaling induces the myogenic specification of resident CD45+ adult stem cells during muscle regeneration.
    Cell. 2003 Jun 27;113(7):841-52 PMID: 12837243
  4. Wnt regulation of chondrocyte differentiation.
    J Cell Sci. 2002 Dec 15;115(Pt 24):4809-18 PMID: 12432069
  5. Castration therapy rapidly induces apoptosis in a minority and decreases cell proliferation in a majority of human prostatic tumors.
    Am J Pathol. 1995 Jun;146(6):1368-75 PMID: 7778676
  6. Molecular determinants of resistance to antiandrogen therapy.
    Nat Med. 2004 Jan;10(1):33-9 PMID: 14702632
  7. Complex regulation of human androgen receptor expression by Wnt signaling in prostate cancer cells.
    Oncogene. 2006 Jun 8;25(24):3436-44 PMID: 16474850
  8. Beta-catenin mutations in human prostate cancer.
    Cancer Res. 1998 Jun 15;58(12):2520-3 PMID: 9635571
  9. The Wnts.
    Genome Biol. 2002;3(1):REVIEWS3001 PMID: 11806834
  10. Identification of a novel protocadherin gene (PCDH11) on the human XY homology region in Xq21.3.
    Genomics. 1999 Dec 15;62(3):540-3 PMID: 10644456
  11. Differentially expressed genes in hormone refractory prostate cancer: association with chromosomal regions involved with genetic aberrations.
    Am J Pathol. 1999 May;154(5):1335-43 PMID: 10329586
  12. The emergence of protocadherin-PC expression during the acquisition of apoptosis-resistance by prostate cancer cells.
    Oncogene. 2002 Nov 7;21(51):7861-71 PMID: 12420223
  13. In vitro evidence for complex modes of nuclear beta-catenin signaling during prostate growth and tumorigenesis.
    Oncogene. 2002 Apr 18;21(17):2679-94 PMID: 11965541
  14. Detection and analysis of beta-catenin mutations in prostate cancer.
    Prostate. 2000 Dec 1;45(4):323-34 PMID: 11102958
  15. Overview of hormonal therapy for prostate cancer.
    Prog Clin Biol Res. 1990;350:129-40 PMID: 2201039
  16. Alteration of the tumor suppressor gene p53 in a high fraction of hormone refractory prostate cancer.
    J Urol. 1995 Aug;154(2 Pt 1):414-21 PMID: 7609105
  17. Blockade of RAGE-amphoterin signalling suppresses tumour growth and metastases.
    Nature. 2000 May 18;405(6784):354-60 PMID: 10830965
  18. Effects of WNT/beta-catenin pathway activation on signaling through T-cell factor and androgen receptor in prostate cancer cell lines.
    Int J Oncol. 2005 Apr;26(4):1033-40 PMID: 15753999
  19. Genetic alterations in prostate cancer.
    Cold Spring Harb Symp Quant Biol. 1994;59:653-9 PMID: 7587126
  20. Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front.
    Oncogene. 2001 Apr 12;20(16):1981-9 PMID: 11360182
  21. The beta-catenin/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells.
    Cell. 2002 Oct 18;111(2):241-50 PMID: 12408868
  22. Immunohistochemical demonstration of phospho-Akt in high Gleason grade prostate cancer.
    Clin Cancer Res. 2002 Apr;8(4):1168-71 PMID: 11948129
  23. A human- and male-specific protocadherin that acts through the wnt signaling pathway to induce neuroendocrine transdifferentiation of prostate cancer cells.
    Cancer Res. 2005 Jun 15;65(12):5263-71 PMID: 15958572
  24. Programmed cell death during regression of PC-82 human prostate cancer following androgen ablation.
    Cancer Res. 1990 Jun 15;50(12):3748-53 PMID: 2340521
  25. The zonal anatomy of the prostate.
    Prostate. 1981;2(1):35-49 PMID: 7279811
  26. Overexpression of bcl-2 protects prostate cancer cells from apoptosis in vitro and confers resistance to androgen depletion in vivo.
    Cancer Res. 1995 Oct 1;55(19):4438-45 PMID: 7671257
  27. APC/CTNNB1 (beta-catenin) pathway alterations in human prostate cancers.
    Genes Chromosomes Cancer. 2002 May;34(1):9-16 PMID: 11921277
  28. Neuroendocrine cell differentiation in the CWR22 human prostate cancer xenograft: association with tumor cell proliferation prior to recurrence.
    Prostate. 2004 Jul 1;60(2):91-7 PMID: 15162375
  29. Beta-catenin-related anomalies in apoptosis-resistant and hormone-refractory prostate cancer cells.
    Clin Cancer Res. 2003 May;9(5):1801-7 PMID: 12738737
  30. Up-regulation of Wnt-1 and beta-catenin production in patients with advanced metastatic prostate carcinoma: potential pathogenetic and prognostic implications.
    Cancer. 2004 Sep 15;101(6):1345-56 PMID: 15316903
  31. A role for Wnt signalling in self-renewal of haematopoietic stem cells.
    Nature. 2003 May 22;423(6938):409-14 PMID: 12717450
  32. Genetic alterations in hormone-refractory recurrent prostate carcinomas.
    Am J Pathol. 1998 Jul;153(1):141-8 PMID: 9665474
  33. Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells.
    Nature. 1999 Apr 1;398(6726):422-6 PMID: 10201372
  34. PPARdelta is an APC-regulated target of nonsteroidal anti-inflammatory drugs.
    Cell. 1999 Oct 29;99(3):335-45 PMID: 10555149
  35. p53 protein accumulation and gene mutation in the progression of human prostate carcinoma.
    J Natl Cancer Inst. 1993 Oct 20;85(20):1657-69 PMID: 7692074
  36. ANX7, a candidate tumor suppressor gene for prostate cancer.
    Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4575-80 PMID: 11287641
  37. A critical review of the concept of total androgen ablation in the treatment of prostate cancer.
    Prog Clin Biol Res. 1987;243A:1-19 PMID: 3309968
  38. Wnt signaling and cancer.
    Genes Dev. 2000 Aug 1;14(15):1837-51 PMID: 10921899
  39. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease.
    Biochemistry. 1979 Nov 27;18(24):5294-9 PMID: 518835
  40. NE-10 neuroendocrine cancer promotes the LNCaP xenograft growth in castrated mice.
    Cancer Res. 2004 Aug 1;64(15):5489-95 PMID: 15289359
  41. Antisense Bcl-2 oligodeoxynucleotides inhibit progression to androgen-independence after castration in the Shionogi tumor model.
    Cancer Res. 1999 Aug 15;59(16):4030-4 PMID: 10463603
  42. Target genes of beta-catenin-T cell-factor/lymphoid-enhancer-factor signaling in human colorectal carcinomas.
    Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1603-8 PMID: 9990071
  43. Regulation of LEF-1/TCF transcription factors by Wnt and other signals.
    Curr Opin Cell Biol. 1999 Apr;11(2):233-40 PMID: 10209158
  44. Hormone-regulated apoptosis results from reentry of differentiated prostate cells onto a defective cell cycle.
    Cancer Res. 1992 Aug 15;52(16):4313-9 PMID: 1353702
  45. Development of androgen resistance in prostatic cancer.
    Prog Clin Biol Res. 1987;243A:21-31 PMID: 3309971
  46. Modulation of cytokeratin subtype, EGF receptor, and androgen receptor expression during progression of prostate cancer.
    Hum Pathol. 1998 Sep;29(9):1005-12 PMID: 9744319
  47. Carcinoma of the prostate.
    N Engl J Med. 1991 Jan 24;324(4):236-45 PMID: 1985245
  48. Identification of c-MYC as a target of the APC pathway.
    Science. 1998 Sep 4;281(5382):1509-12 PMID: 9727977
  49. The Wnt signaling pathway and its role in tumor development.
    J Cancer Res Clin Oncol. 2003 Apr;129(4):199-221 PMID: 12707770
  50. The development of androgen-independent prostate cancer.
    Nat Rev Cancer. 2001 Oct;1(1):34-45 PMID: 11900250
  51. Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer.
    Cancer Res. 2001 Dec 15;61(24):8664-7 PMID: 11751382
  52. Stem cells of the skin epithelium.
    Proc Natl Acad Sci U S A. 2003 Sep 30;100 Suppl 1:11830-5 PMID: 12913119
  53. Conservation of PCDHX in mammals; expression of human X/Y genes predominantly in brain.
    Mamm Genome. 2000 Oct;11(10):906-14 PMID: 11003707
  54. Carcinoma of the prostate. Hormonal therapy.
    Cancer. 1987 Aug 1;60(3 Suppl):589-601 PMID: 3297288
  55. Evidence for clonal outgrowth of androgen-independent prostate cancer cells from androgen-dependent tumors through a two-step process.
    Cancer Res. 1999 Oct 1;59(19):5030-6 PMID: 10519419
Article Info
Journal
The Prostate
Abbr.
Prostate
ISSN
0270-4137
Published
2006-07-01
Pages
1100-13
Language
English
Region
United States
NLM ID
8101368
PMCID
PMC2660890
Subset
IM
Grants
NCI NIH HHS · R01 CA111618 · United States
NCI NIH HHS · R01 CA111618-04 · United States
NCI NIH HHS · CA111618 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com