Transcript PTEN (Cowden Syndrome)

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