Loss of PTEN Regulator Linked to Cancer

A recent study describes the electrostatic mechanism that controls the binding of the tumor-suppressing protein PTEN (phosphatase and tensin homolog on chromosome 10) to the cell membrane.

PTEN is a tumor suppressor that reverses the action of phosphoinositide 3-kinase by catalyzing the removal of the 3' phosphate of phosphoinositides. "The role of PTEN is to counterbalance the action of an enzyme that induces cell growth,” explained senior author Dr. Wonhwa Cho, professor of chemistry at the University of Chicago (IL, USA; www.uic.edu). "Overactivation of the enzyme can lead to cancer. So if you lose a PTEN gene and its cellular activity, the cell goes out of control. It is like a car with an accelerator but without the brakes.”

The investigators employed surface plasmon resonance analysis and cellular microscopic analysis of green fluorescence protein-labeled PTEN to study its transport and binding within the cell. They found that phosphorylation of PTEN changed its electrostatic property. Once it switched from being electrostatically neutral to being positively charged, PTEN attached to negatively charged molecules on the cell membrane. These findings were published June 13, 2003, in the online edition of the Proceedings of the National Academy of Science.

Mutations resulting in the loss of PTEN regulation have been linked to various cancers, including glioblastoma, endometrial carcinoma, and a cancer-prone condition called Cowden disease.