Cadherin-7 Gene Amplification is Associated with Prostate Cancer
The incidence of prostate cancer continues to rise. One in six men is diagnosed with prostate cancer, which accounts for 30,000 deaths per year in the U.S. Still, prostate cancer diagnosis has not improved appreciably in the past decade. Prostate-specific antigen (PSA) is used for the early detection of prostate cancer, however, a prevalence of prostate cancer was recently reported in men with “normal” PSA levels—emphasizing the importance of identifying sensitive biomarkers for detecting prostate cancer. The purpose of this study was to identify regions of loss and gain in prostate cancer tissue on chromosome 18q, a chromosome which suppresses prostate cancer tumorigenicity and metastases. A copy number amplification of chromosome 18q22.1, containing the gene for cadherin-7 (CDH7), was observed in several primary prostate tumors. Amplification of CDH7 was confirmed by FISH and real-time quantitative PCR. By FISH, three or more copies of CDH7 were observed in 60 out of 60 prostate tumors, as well as testicular cancer, but not adjacent/control tissues or other cancers. All prostate tumor stages and grades showed amplification of CDH7. Because cadherin-7 may be associated with changes in cell adhesion related to invasion and metastases of cancer cells, we initiated an examination of the functional role of this protein in cancer specimens and a prostate cancer cell-line, 22RV1. First, an antibody specific to cadherin-7 was generated and used to screen and score normal and prostate cancer specimens. Stable RNA interference will be used to knockdown expression of cadherin-7 and analyze the transformed/metastatic phenotype of prostate cancer cells using in vitro assays for anchorage independence and migration/invasion. Based on these studies, cadherin-7 may be an important and novel biomarker. The amplification of CDH7 at all stages of prostate cancer suggests this is an early event and, therefore, a promising marker for the early detection of prostate cancer.