Overexpression of Serine Proteases in Ovarian Cancer

Shelley Campeau Cellular and Developmental Biology Major University of California at Santa Barbara

Figure 1. Female reproductive organs [Campbell, 1998].

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

Definition: Cancer that forms in the cells surrounding the ovaries.

• 5 year survival rate for women with ovarian cancer is below 50%

Figure 2. Stains of a normal ovary and an ovarian tumor for serine proteases [Underwood, 2000].

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 spreadingof 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

+ SerineProteases

Tumor cell growthand progression of

cancer.

Then:

Normal cells

+ InhibitedSerine

Proteases

PREVENTTUMOR

GROWTH!

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

Results: Band size of serine protease expression is found inovarian cancer tissue but not in normal ovary tissue.

Figure 4. PCR for a serine protease. Normal ovary in left lane, ovarian tumorin right lane [Underwood, 2000].

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 significantlevels 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.