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