Logo of brjcancerBJC HomepageBJC Advance online publicationBJC Current IssueSubmitting an article to BJCWeb feeds
Br J Cancer. 1998; 77(2): 319–324.
PMCID: PMC2151239

High expression of Wnt7b in human superficial bladder cancer vs invasive bladder cancer.


Aberrant Wnt gene expression is involved in the development of breast cancer, but its role in other tumours is unknown. Wnts regulate cadherin function, previously shown to be more commonly deregulated in invasive bladder cancer. This study investigated whether factors upstream of cadherins were aberrantly expressed in superficial bladder cancer. The expression of one transforming (Wnt7b) and one non-transforming (Wnt5a) Wnt gene in four human bladder carcinoma cell lines, and in normal human bladder tissues (n = 8) and bladder cancers (n = 48) were analysed by ribonuclease protection analysis. All cell lines expressed an approximately equal level of Wnt7b mRNA. Wnt5a and Wnt7b mRNAs were both expressed in normal bladder tissues and bladder tumours. The median expression of Wnt7b was fourfold higher in superficial tumours (n = 29) than in normal tissues (n = 8, P = 0.002) and five fold higher than in invasive tumours (n = 17, P = 0.003). There was no significant difference between normal tissues and invasive tumours (P = 0.3). The expression of Wnt5a did not vary significantly between normal tissues and superficial tumours (P = 0.4), normal tissues and invasive tumours (P = 0.3) or superficial tumours and invasive tumours (P = 0.2). The differential expression of Wnt7b suggests a role in the early events of superficial bladder tumorigenesis involving cell adhesion and provides further evidence of different pathways of evolution of superficial and invasive cancer.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Bradley RS, Brown AM. The proto-oncogene int-1 encodes a secreted protein associated with the extracellular matrix. EMBO J. 1990 May;9(5):1569–1575. [PMC free article] [PubMed]
  • Bradley RS, Brown AM. A soluble form of Wnt-1 protein with mitogenic activity on mammary epithelial cells. Mol Cell Biol. 1995 Aug;15(8):4616–4622. [PMC free article] [PubMed]
  • Bradley RS, Cowin P, Brown AM. Expression of Wnt-1 in PC12 cells results in modulation of plakoglobin and E-cadherin and increased cellular adhesion. J Cell Biol. 1993 Dec;123(6 Pt 2):1857–1865. [PMC free article] [PubMed]
  • Bringuier PP, Umbas R, Schaafsma HE, Karthaus HF, Debruyne FM, Schalken JA. Decreased E-cadherin immunoreactivity correlates with poor survival in patients with bladder tumors. Cancer Res. 1993 Jul 15;53(14):3241–3245. [PubMed]
  • Brown AM, Papkoff J, Fung YK, Shackleford GM, Varmus HE. Identification of protein products encoded by the proto-oncogene int-1. Mol Cell Biol. 1987 Nov;7(11):3971–3977. [PMC free article] [PubMed]
  • Burrus LW, McMahon AP. Biochemical analysis of murine Wnt proteins reveals both shared and distinct properties. Exp Cell Res. 1995 Oct;220(2):363–373. [PubMed]
  • Clark CC, Cohen I, Eichstetter I, Cannizzaro LA, McPherson JD, Wasmuth JJ, Iozzo RV. Molecular cloning of the human proto-oncogene Wnt-5A and mapping of the gene (WNT5A) to chromosome 3p14-p21. Genomics. 1993 Nov;18(2):249–260. [PubMed]
  • Fagotto F, Gumbiner BM. Cell contact-dependent signaling. Dev Biol. 1996 Dec 15;180(2):445–454. [PubMed]
  • Griffiths TR, Brotherick I, Bishop RI, White MD, McKenna DM, Horne CH, Shenton BK, Neal DE, Mellon JK. Cell adhesion molecules in bladder cancer: soluble serum E-cadherin correlates with predictors of recurrence. Br J Cancer. 1996 Aug;74(4):579–584. [PMC free article] [PubMed]
  • Hinck L, Nelson WJ, Papkoff J. Wnt-1 modulates cell-cell adhesion in mammalian cells by stabilizing beta-catenin binding to the cell adhesion protein cadherin. J Cell Biol. 1994 Mar;124(5):729–741. [PMC free article] [PubMed]
  • Huguet EL, McMahon JA, McMahon AP, Bicknell R, Harris AL. Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue. Cancer Res. 1994 May 15;54(10):2615–2621. [PubMed]
  • Huguet EL, Smith K, Bicknell R, Harris AL. Regulation of Wnt5a mRNA expression in human mammary epithelial cells by cell shape, confluence, and hepatocyte growth factor. J Biol Chem. 1995 May 26;270(21):12851–12856. [PubMed]
  • Iozzo RV, Eichstetter I, Danielson KG. Aberrant expression of the growth factor Wnt-5A in human malignancy. Cancer Res. 1995 Aug 15;55(16):3495–3499. [PubMed]
  • Kitajewski J, Mason JO, Varmus HE. Interaction of Wnt-1 proteins with the binding protein BiP. Mol Cell Biol. 1992 Feb;12(2):784–790. [PMC free article] [PubMed]
  • Knowles MA, Elder PA, Williamson M, Cairns JP, Shaw ME, Law MG. Allelotype of human bladder cancer. Cancer Res. 1994 Jan 15;54(2):531–538. [PubMed]
  • Kühl M, Wedlich D. Wnt signalling goes nuclear. Bioessays. 1997 Feb;19(2):101–104. [PubMed]
  • Lejeune S, Huguet EL, Hamby A, Poulsom R, Harris AL. Wnt5a cloning, expression, and up-regulation in human primary breast cancers. Clin Cancer Res. 1995 Feb;1(2):215–222. [PubMed]
  • Mason JO, Kitajewski J, Varmus HE. Mutational analysis of mouse Wnt-1 identifies two temperature-sensitive alleles and attributes of Wnt-1 protein essential for transformation of a mammary cell line. Mol Biol Cell. 1992 May;3(5):521–533. [PMC free article] [PubMed]
  • McCarthy SA, Bicknell R. Responses of pertussis toxin-treated microvascular endothelial cells to transforming growth factor beta 1. No evidence for pertussis-sensitive G-protein involvement in TGF-beta signal transduction. J Biol Chem. 1992 Oct 25;267(30):21617–21622. [PubMed]
  • Moon RT, Campbell RM, Christian JL, McGrew LL, Shih J, Fraser S. Xwnt-5A: a maternal Wnt that affects morphogenetic movements after overexpression in embryos of Xenopus laevis. Development. 1993 Sep;119(1):97–111. [PubMed]
  • Neal DE, Sharples L, Smith K, Fennelly J, Hall RR, Harris AL. The epidermal growth factor receptor and the prognosis of bladder cancer. Cancer. 1990 Apr 1;65(7):1619–1625. [PubMed]
  • Nusse R, Varmus HE. Wnt genes. Cell. 1992 Jun 26;69(7):1073–1087. [PubMed]
  • O'Brien T, Cranston D, Fuggle S, Bicknell R, Harris AL. Different angiogenic pathways characterize superficial and invasive bladder cancer. Cancer Res. 1995 Feb 1;55(3):510–513. [PubMed]
  • Papkoff J. Inducible overexpression and secretion of int-1 protein. Mol Cell Biol. 1989 Aug;9(8):3377–3384. [PMC free article] [PubMed]
  • Papkoff J, Schryver B. Secreted int-1 protein is associated with the cell surface. Mol Cell Biol. 1990 Jun;10(6):2723–2730. [PMC free article] [PubMed]
  • Papkoff J, Brown AM, Varmus HE. The int-1 proto-oncogene products are glycoproteins that appear to enter the secretory pathway. Mol Cell Biol. 1987 Nov;7(11):3978–3984. [PMC free article] [PubMed]
  • Parr BA, McMahon AP. Dorsalizing signal Wnt-7a required for normal polarity of D-V and A-P axes of mouse limb. Nature. 1995 Mar 23;374(6520):350–353. [PubMed]
  • Presti JC, Jr, Reuter VE, Galan T, Fair WR, Cordon-Cardo C. Molecular genetic alterations in superficial and locally advanced human bladder cancer. Cancer Res. 1991 Oct 1;51(19):5405–5409. [PubMed]
  • Roelink H, Wang J, Black DM, Solomon E, Nusse R. Molecular cloning and chromosomal localization to 17q21 of the human WNT3 gene. Genomics. 1993 Sep;17(3):790–792. [PubMed]
  • Shimazui T, Schalken JA, Giroldi LA, Jansen CF, Akaza H, Koiso K, Debruyne FM, Bringuier PP. Prognostic value of cadherin-associated molecules (alpha-, beta-, and gamma-catenins and p120cas) in bladder tumors. Cancer Res. 1996 Sep 15;56(18):4154–4158. [PubMed]
  • Syrigos KN, Krausz T, Waxman J, Pandha H, Rowlinson-Busza G, Verne J, Epenetos AA, Pignatelli M. E-cadherin expression in bladder cancer using formalin-fixed, paraffin-embedded tissues: correlation with histopathological grade, tumour stage and survival. Int J Cancer. 1995 Dec 20;64(6):367–370. [PubMed]
  • Stark K, Vainio S, Vassileva G, McMahon AP. Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4. Nature. 1994 Dec 15;372(6507):679–683. [PubMed]
  • van Ooyen A, Kwee V, Nusse R. The nucleotide sequence of the human int-1 mammary oncogene; evolutionary conservation of coding and non-coding sequences. EMBO J. 1985 Nov;4(11):2905–2909. [PMC free article] [PubMed]
  • Vet JA, Debruyne FM, Schalken JA. Molecular prognostic factors in bladder cancer. World J Urol. 1994;12(2):84–88. [PubMed]
  • Vider BZ, Zimber A, Chastre E, Prevot S, Gespach C, Estlein D, Wolloch Y, Tronick SR, Gazit A, Yaniv A. Evidence for the involvement of the Wnt 2 gene in human colorectal cancer. Oncogene. 1996 Jan 4;12(1):153–158. [PubMed]
  • Wainwright BJ, Scambler PJ, Stanier P, Watson EK, Bell G, Wicking C, Estivill X, Courtney M, Boue A, Pedersen PS, et al. Isolation of a human gene with protein sequence similarity to human and murine int-1 and the Drosophila segment polarity mutant wingless. EMBO J. 1988 Jun;7(6):1743–1748. [PMC free article] [PubMed]
  • Wakatsuki S, Watanabe R, Saito K, Saito T, Katagiri A, Sato S, Tomita Y. Loss of human E-cadherin (ECD) correlated with invasiveness of transitional cell cancer in the renal pelvis, ureter and urinary bladder. Cancer Lett. 1996 May 15;103(1):11–17. [PubMed]
  • Whitehead I, Kirk H, Kay R. Expression cloning of oncogenes by retroviral transfer of cDNA libraries. Mol Cell Biol. 1995 Feb;15(2):704–710. [PMC free article] [PubMed]
  • Witjes JA, Umbas R, Debruyne FM, Schalken JA. Expression of markers for transitional cell carcinoma in normal bladder mucosa of patients with bladder cancer. J Urol. 1995 Dec;154(6):2185–2189. [PubMed]
  • Wong GT, Gavin BJ, McMahon AP. Differential transformation of mammary epithelial cells by Wnt genes. Mol Cell Biol. 1994 Sep;14(9):6278–6286. [PMC free article] [PubMed]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem chemical compound records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records. Multiple substance records may contribute to the PubChem compound record.
  • Gene
    Gene records that cite the current articles. Citations in Gene are added manually by NCBI or imported from outside public resources.
  • Gene (nucleotide)
    Gene (nucleotide)
    Records in Gene identified from shared sequence and PMC links.
  • GEO Profiles
    GEO Profiles
    Gene Expression Omnibus (GEO) Profiles of molecular abundance data. The current articles are references on the Gene record associated with the GEO profile.
  • HomoloGene
    HomoloGene clusters of homologous genes and sequences that cite the current articles. These are references on the Gene and sequence records in the HomoloGene entry.
  • MedGen
    Related information in MedGen
  • Nucleotide
    Primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • Protein
    Protein translation features of primary database (GenBank) nucleotide records reported in the current articles as well as Reference Sequences (RefSeqs) that include the articles as references.
  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...