Review on WFDC1 (WAP four-disulfide core domain 1), with data on DNA, on the protein encoded, and where the gene is implicated

Debuire, B

Lemoine, A

Saffroy, R

Atlas of Genetics and Cytogenetics in Oncology and Haematology

I-Revues

   
 
 
 
 
 
Gene Section 
Mini Review 
 
Atlas Genet Cytogenet Oncol Haematol. 2005; 9(4)  
 
283 
Atlas of Genetics and Cytogenetics 
in Oncology and Haematology 
OPEN ACCESS JOURNAL AT INIST-CNRS 
WFDC1 (WAP four-disulfide core domain 1) 
Raphaël Saffroy, Antoinette Lemoine, Brigitte Debuire 
Service de Biochimie et Biologie moléculaire, Hôpital Universitaire Paul Brousse, 14 avenue Paul Vaillant 
Couturier, 94800 Villejuif, France (RS, AL, BD) 
 
Published in Atlas Database: June 2005 
Online updated version: http://AtlasGeneticsOncology.org/Genes/WFDC1ID424.html 
DOI: 10.4267/2042/38237 
This article is an update of: Saffroy R, Lemoine A, Debuire B. WFDC1 (WAP four-disulfide core domain 1). Atlas Genet Cytogenet Oncol 
Haematol.2003;7(2):103-104. 
 
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. 
© 2005 Atlas of Genetics and Cytogenetics in Oncology and Haematology 
 
Identity 
Other names: ps20 
HGNC (Hugo): WFDC1 
Location: 16q24.1 
DNA/RNA 
Description 
The gene encompasses 35 kb of DNA; 7 exons. 
Transcription 
1366 nucleotides mRNA; 660 bp open reading frame. 
Protein 
Description 
220 amino acids; 24 kDa protein. Like rat ps20, human 
ps20 protein contains a WAP signature domain. 
Expression 
Widely expressed, absent in thymus. 
Function 
The rat homologue of ps20 was originally identified as 
a secreted growth inhibitor. These growth regulatory 
effects and the cell phenotypic properties in vitro, 
suggest that ps20 may function as a mediator of 
stromal-epithelial interactions and contribute to the 
maintenance of tissue homeostasis. The ps20 protein is 
assumed to function as a protease inhibitor. In vitro 
studies indicate that exogeneous addition of ps20 
protein stimulates endothelial cell migration, and 
promotes angiogenesis and tumour growth in a 
xenograft model of prostate cancer. 
Homology 
The human WFDC1 protein shares approximately 86% 
and 88% identity with the rat and mouse proteins, 
respectively. WFDC1 is related to a family of human 
proteins that also have homology with WAP. The 
WFDC1 gene organization presents similarities with 
that of the KAL gene, which extends on 210 kb of 
DNA, includes 14 exons and is the largest gene in the 
WAP signature domain family. 
 
Representation of the position of the conserved cysteines for the category of "four-disulfide core" domain and the location of the signature 
pattern for such a domain in the human WFDC1 amino acid sequence. 
 
 
WFDC1 (WAP four-disulfide core domain 1) Saffroy R, et al. 
 
Atlas Genet Cytogenet Oncol Haematol. 2005; 9(4)  
 
284 
Mutations 
Note 
Although WFDC1 was mapped to human chromosome 
16q24, an area of frequent loss of heterozygosity 
(LOH) in prostate and hepatocellular carcinomas, no 
tumour-associated mutations were identified in the 
coding region of WFDC1 in these cancer types. 
Mutations in WFDC1 gene resulting in Gly9Asp, 
Pro211Ser and Lys217Arg substitutions have been 
found at low frequency in the stroma of breast 
carcinomas. One mutation resulting in a Pro167Ser 
substitution has been identified in the epithelium of 
breast carcinoma. 
Implicated in 
Disease 
Prostate cancer 
Oncogenesis 
WFDC1 is significantly down-regulated in prostate 
cancer making it a candidate tumour suppressor gene. 
However, WFDC1 seems predominantly expressed in 
the stroma of normal prostate. In tumors, decreased 
stromal WFDC1 expression has been associated with 
increased epithelial WFDC1 expression. This correlates 
with shorter recurrence-free survival times and may 
indicate progression to a more aggressive epithelial 
phenotype and an epithelial mesenchymal transition 
process. 
References 
Rowley DR, Tindall DJ. Responses of NBT-II bladder 
carcinoma cells to conditioned medium from normal fetal 
urogenital sinus. Cancer Res. 1987 Jun 1;47(11):2955-60 
Rowley DR. Characterization of a fetal urogenital sinus 
mesenchymal cell line U4F: secretion of a negative growth 
regulatory activity. In Vitro Cell Dev Biol. 1992 Jan;28A(1):29-
38 
Rowley DR, Dang TD, Larsen M, Gerdes MJ, McBride L, Lu B. 
Purification of a novel protein (ps20) from urogenital sinus 
mesenchymal cells with growth inhibitory properties  
in vitro. J Biol Chem. 1995 Sep 15;270(37):22058-65 
Larsen M, Ressler SJ, Lu B, Gerdes MJ, McBride L, Dang TD, 
Rowley DR. Molecular cloning and expression of ps20 growth 
inhibitor. A novel WAP-type "four-disulfide core" domain 
protein expressed in smooth muscle. J Biol Chem. 1998 Feb 
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Larsen M, Ressler SJ, Gerdes MJ, Lu B, Byron M, Lawrence 
JB, Rowley DR. The WFDC1 gene encoding ps20 localizes to 
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Lemoine A. Analysis of alterations of WFDC1, a new putative 
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expression and increased epithelial expression of 
WFDC1/ps20 in prostate cancer is associated with reduced 
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This article should be referenced as such: 
Saffroy R, Lemoine A, Debuire B. WFDC1 (WAP four-disulfide 
core domain 1). Atlas Genet Cytogenet Oncol Haematol. 2005; 
9(4):283-284. 


WFDC1 (WAP four-disulfide core domain 1)

http://documents.irevues.inist.fr/bitstream/2042/38237/3/06-2005-WFDC1ID424.pdf

WFDC1 (WAP four-disulfide core domain 1)

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