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The WFDC1 gene encoding ps20 localizes to 16q24, a region of LOH in multiple cancers
M Larsen1, S J Ressler, M J Gerdes
1Cell and Molecular Biology Program, Baylor College of Medicine, Houston, Texas 77030, USA.
Abstract:
We previously identified ps20 protein as a secreted growth inhibitor and purified the protein from fetal rat prostate urogenital sinus mesenchymal cell conditioned medium. The rat cDNA was subsequently cloned, and ps20 was found to contain a WAP-type four-disulfide core motif, indicating it may function as a protease inhibitor. We now report cloning and characterization of the mouse ps20 gene (designated Wfdc1), the human homolog cDNA, and the human gene (designated WFDC1). Both the mouse and human WFDC1 genes consist of seven exons and encode respective ps20 proteins sharing 79.1% identity and nearly identical WAP motifs in exon 2. The WFDC1 gene was mapped by FISH analysis to human Chromosome (Chr) 16q24, an area of frequent loss of heterozygosity (LOH) previously identified in multiple cancers including prostate, breast, hepatocellular, and Wilms' tumor. Identification and characterization of the WFDC1 gene may aid in better understanding the potential role of this gene and ps20 in prostate biology and carcinogenesis.
Insights
Researchers identified the mouse and human WFDC1 genes, homologs of the ps20 protein. The WFDC1 gene
Area of Science:
- Molecular Biology
- Genetics
- Cancer Research
Background:
- The ps20 protein was previously identified as a secreted growth inhibitor in rat prostate mesenchymal cells.
- Ps20 contains a WAP-type four-disulfide core motif, suggesting a role as a protease inhibitor.
Purpose of the Study:
- To clone and characterize the mouse ps20 gene (Wfdc1) and its human homolog (WFDC1).
- To investigate the potential role of WFDC1 and ps20 in prostate biology and cancer.
Main Methods:
- Cloning of mouse Wfdc1 and human WFDC1 cDNA and gene.
- Sequence analysis and comparison of mouse and human WFDC1.
- Fluorescence in situ hybridization (FISH) for gene mapping.
Main Results:
- The mouse Wfdc1 and human WFDC1 genes consist of seven exons.
- Mouse and human ps20 proteins share 79.1% identity with nearly identical WAP motifs.
- The human WFDC1 gene was mapped to Chromosome 16q24, a region associated with LOH in various cancers.
Conclusions:
- The characterization of the WFDC1 gene provides a foundation for understanding its function.
- WFDC1's location on Chr 16q24 suggests a potential role in carcinogenesis, particularly in prostate cancer.
- Further research into WFDC1 and ps20 may elucidate their involvement in prostate development and disease.