Atlas of Genetics and Cytogenetics in Oncology and Haematology
WFDC1 (WAP four-disulfide core domain 1)
| Identity |
| Other names | ps20 |
| HGNC | 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 |
 | |
| 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. | |
| 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. |
| 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 correlate with shorter recurrence-free survival times and may indicate progression to a more aggressive epithelial phenotype and an epithelial mesenchymal transition process. |
| External links |
| Bibliography |
| Responses of NBT-II bladder carcinoma cells to conditioned medium from normal fetal urogenital sinus. |
| Rowley DR, Tindall DJ |
| Cancer research. 1987 ; 47 (11) : 2955-2960. |
| PMID 3567912 |
| Characterization of a fetal urogenital sinus mesenchymal cell line U4F: secretion of a negative growth regulatory activity. |
| Rowley DR |
| In vitro cellular & developmental biology : journal of the Tissue Culture Association. 1992 ; 28A (1) : 29-38. |
| PMID 1730568 |
| Purification of a novel protein (ps20) from urogenital sinus mesenchymal cells with growth inhibitory properties in vitro. |
| Rowley DR, Dang TD, Larsen M, Gerdes MJ, McBride L, Lu B |
| The Journal of biological chemistry. 1995 ; 270 (37) : 22058-22065. |
| PMID 7665628 |
| Molecular cloning and expression of ps20 growth inhibitor. A novel WAP-type four-disulfide core domain protein expressed in smooth muscle. |
| Larsen M, Ressler SJ, Lu B, Gerdes MJ, McBride L, Dang TD, Rowley DR |
| The Journal of biological chemistry. 1998 ; 273 (8) : 4574-4584. |
| PMID 9468514 |
| The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple cancers. |
| Larsen M, Ressler SJ, Gerdes MJ, Lu B, Byron M, Lawrence JB, Rowley DR |
| Mammalian genome : official journal of the International Mammalian Genome Society. 2000 ; 11 (9) : 767-773. |
| PMID 10967136 |
| Frequent somatic mutations in PTEN and TP53 are mutually exclusive in the stroma of breast carcinomas. |
| Kurose K, Gilley K, Matsumoto S, Watson PH, Zhou XP, Eng C |
| Nature genetics. 2002 ; 32 (3) : 355-357. |
| PMID 12379854 |
| Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma. |
| Saffroy R, Riou P, Soler G, Azoulay D, Emile JF, Debuire B, Lemoine A |
| European journal of human genetics : EJHG. 2002 ; 10 (4) : 239-244. |
| PMID 12032731 |
| Promotion of angiogenesis by ps20 in the differential reactive stroma prostate cancer xenograft model. |
| McAlhany SJ, Ressler SJ, Larsen M, Tuxhorn JA, Yang F, Dang TD, Rowley DR |
| Cancer research. 2003 ; 63 (18) : 5859-5865. |
| PMID 14522910 |
| Integration of high-resolution array comparative genomic hybridization analysis of chromosome 16q with expression array data refines common regions of loss at 16q23-qter and identifies underlying candidate tumor suppressor genes in prostate cancer. |
| Watson JE, Doggett NA, Albertson DG, Andaya A, Chinnaiyan A, van Dekken H, Ginzinger D, Haqq C, James K, Kamkar S, Kowbel D, Pinkel D, Schmitt L, Simko JP, Volik S, Weinberg VK, Paris PL, Collins C |
| Oncogene. 2004 ; 23 (19) : 3487-3494. |
| PMID 15007382 |
| Decreased stromal expression and increased epithelial expression of WFDC1/ps20 in prostate cancer is associated with reduced recurrence-free survival. |
| McAlhany SJ, Ayala GE, Frolov A, Ressler SJ, Wheeler TM, Watson JE, Collins C, Rowley DR |
| The Prostate. 2004 ; 61 (2) : 182-191. |
| PMID 15305341 |
| Molecular analysis of WFDC1/ps20 gene in prostate cancer. |
| Watson JE, Kamkar S, James K, Kowbel D, Andaya A, Paris PL, Simko J, Carroll P, McAlhany S, Rowley D, Collins C |
| The Prostate. 2004 ; 61 (2) : 192-199. |
| PMID 15305342 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 03-2003 | Raphael Saffroy, Antoinette Lemoine, Brigitte Debuire |
| Updated | 06-2005 | Raphael Saffroy, Antoinette Lemoine, Brigitte Debuire |
| Citation |
| This paper should be referenced as such : |
| Saffroy R, Lemoine A, Debuire B . WFDC1 (WAP four-disulfide core domain 1). Atlas Genet Cytogenet Oncol Haematol. March 2003 . URL : http://AtlasGeneticsOncology.org/Genes/WFDC1ID424.html |
| Saffroy R, Lemoine A, Debuire B . WFDC1 (WAP four-disulfide core domain 1). Atlas Genet Cytogenet Oncol Haematol. June 2005 . URL : http://AtlasGeneticsOncology.org/Genes/WFDC1ID424.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Mon Aug 11 21:18:26 2008 |
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