1. PTEN (Cowden Syndrome) 140.116.60.1/.../ sld083.htm

2. Cellular Machinery Protein Product of PTEN is a phosphatase Similar to cdc 25 in S. pombe, but acts on the Cyclin D1/protein-tyrosine kinase pathway Acts as a tumor suppressor PTEN  Biology 169; Spring 2004 Lecture Notes

3. Where does it act? ALMOST EVERYWHERE!!!!!! Sulis et al; PTEN: from pathology to biology

4. PTEN MODULATES G1 CELL CYCLE PROGRESSION Inhibits cells from entering s phase Biology 169; Spring 2004 Lecture Notes

5. Normal Biological Role? Let’s Look at some knockout mutations in mice….

6. PTEN -/- Mutation in Mice Mouse not viable. WHY??? Cells could not differentiate into ectoderm, mesoderm, and ectoderm What does this tell us about PTEN’s role in the cell?

7. FUNCTION OF PTEN PTEN is necessary for development in mice PTEN +/- mice are viable, but adults develop a variety of tumors The same is true for humans as well www.rit.edu/~sbib350/posters/ reoresults.htm

8. Much is still unknown… We know that PTEN phosphorylates other proteins in the cell, but what else do we know PTEN is involved with? –Cell signaling (including apoptosis) –Cell migration (actin filament degradation?) –Cell adhesion (to surrounding tissues) But HOW is still mostly a mystery

9. PTEN AND CANCER Tumor Suppressor Patients develop HAMARTOMAS http://www.emedicine.com/derm/topic428.htm#section~pictures

10. Hamartomas Multiple tumor-like growths - Same tissue as its location With Cowden Syndrome, these growths become malignant tumors perso.wanadoo.fr/docpjw/ cowden.htm

11. PTEN INHERITANCE Autosomal dominant pattern of inheritance, yet recessive at cellular level - similar to Rb Rbhttp://www.baylorcme.org/breastcancer/presentations/plon/images

12. Where does CS hit? Just about everywhere –Thyroid –Breast –Skin –Uterus –Lungs –Throat and many more –Occurs in about 1/200,000 people

13. Current Treatment Options Retinoids –Temporary control over lesions caused by CS Traditional chemotherapy and radiation –Effective if caught in very early stages www.vh.org/.../1-Esophagus/ PolypsImage1.html