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PTEN (Cowden Syndrome). 140.116.60.1/.../ sld083.htm. 140.116.60.1/.../ sld083.htm. 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 .
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PTEN (Cowden Syndrome) 140.116.60.1/.../ sld083.htm 140.116.60.1/.../ sld083.htm
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
Where does it act? ALMOST EVERYWHERE!!!!!! Sulis et al; PTEN: from pathology to biology
PTEN MODULATES G1 CELL CYCLE PROGRESSION • Inhibits cells from entering s phase Biology 169; Spring 2004 Lecture Notes
Normal Biological Role? • Let’s Look at some knockout mutations in mice….
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?
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
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
PTEN AND CANCER • Tumor Suppressor • Patients develop HAMARTOMAS • http://www.emedicine.com/derm/topic428.htm#section~pictures
Hamartomas • Multiple tumor-like growths - Same tissue as its location • With Cowden Syndrome, these growths become malignant tumors perso.wanadoo.fr/docpjw/ cowden.htm
PTEN INHERITANCE • Autosomal dominant pattern of inheritance, yet recessive at cellular level - similar to Rb Rbhttp://www.baylorcme.org/breastcancer/presentations/plon/images
Where does CS hit? • Just about everywhere • Thyroid • Breast • Skin • Uterus • Lungs • Throat and many more • Occurs in about 1/200,000 people
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