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Overexpression of Serine Proteases in Ovarian Cancer Figure 1. Female reproductive organs [Campbell, 1998]. Shelley Campeau Cellular and Developmental Biology Major University of California at Santa Barbara Topics • Overview of ovarian cancer • Role of serine proteases in ovarian tumor growth • Two experiments showing serine protease expression in ovarian cancer Why Study Serine Proteases? Allows growth and spread of ovarian cancer. Produced early in tumor formation and can be detected early. Inhibiting serine proteases may possibly stop ovarian tumor formation. Overview: Ovarian Cancer Cancer that forms in the cells surrounding the ovaries. Figure 2. Stains of a normal ovary and an ovarian tumor for serine proteases [Underwood, 2000]. 5 year survival rate for women with ovarian cancer is below 50% How Ovarian Cancer Invades Initiates development around ovaries. Tumor cells can break off and spread to other sites. Secondary tumors can form. Figure 3. Metastasis and the spreading of cancer [McKinnell, 1998]. Role of Serine Proteases What are they? Enzymes involved in the breakdown of proteins in extracellular compartments. Function in tumor growth Breakdown extracellular components surrounding ovaries Allows tumor cells to rapidly divide Tumor cells can break off and travel to different locations to spread cancer Serine Proteases: Potential for Diagnosis and Treatment If: Normal cells + Serine Proteases Tumor cell growth and progression of cancer. PREVENT TUMOR GROWTH! Then: Normal cells + Inhibited Serine Proteases Experiment 1: Polymerase Chain Reaction (PCR) Process Amplify serine protease gene from ovarian tumor and normal ovary tissue. Separate products obtained from experiment based on size. Look for band size of serine protease expression: 180bp Figure 4. PCR for a serine protease. Normal ovary in left lane, ovarian tumor in right lane [Underwood, 2000]. Results Band size of serine protease expression is found in ovarian cancer tissue but not in normal ovary tissue. Experiment 2: Northern Blot Analyses Process: Separates RNA fragments of a tissue sample based on size. A probe for a specific region of RNA hybridizes to the corresponding fragment. TADG Testisin Figure 5. Northern blot analyses of serine proteases: TADG [Underwood, 2000] and Testisin [Shigemasa,2000]. Results: Bands found in ovarian cancer tissue and not in significant levels in normal ovary tissue. Conclusion Serine proteases aid in the development of ovarian cancer. Used as a tumor marker, serine proteases may be used to help identify cancer before it is too late.