Understanding Genetic Mutations and the Effect on Tumor Growth

Researchers evaluate how PTEN protein regulates cell growth and how mutations can lead to cancer.

A new avenue for cancer therapy may open up thanks to a new discovery regarding phosphatase and tensin homolog (PTEN) genes.

A recent study provides new insights into how the PTEN protein regulates cell growth and how mutations in the gene that encodes the protein can lead to cancer.

PTEN is a known tumor suppressing protein that is encoded by the PTEN gene. When released at normal levels, the protein acts as an enzyme at the cell membrane, starting a complex biochemical reaction that regulates the cell cycle and prevents cells from growing or dividing in an unregulated fashion.

There are two types of PTEN genes within everyone’s body: one from the mother and one from the father. When a mutation occurs in one or both of them, it interferes with the protein’s ability to suppress tumors.

“Membrane-incorporated and membrane-associated proteins like PTEN make up one-third of all proteins in our body. Many important functions in health and disease depend on their proper functioning,” said physicist Mathias Losche from Carnegie Mellon University. “Despite PTEN’s importance in human physiology and disease, there is a critical lack of understanding of the complex mechanisms that govern its activity.”

Recently, researchers at Harvard Medical School found that PTEN’s ability to suppress tumors increases with the binding of 2 copies of the protein, forming a dimeric protein.

“PTEN dimerization may be the key to understanding an individual’s susceptibility for PTEN-sensitive tumors,” said Losche, a professor of physics and biomedical engineering at Carnegie Mellon.

In order to reveal the effects of dimerization in PTEN, researchers needed to establish the protein’s dimeric structure. Traditionally, protein structure is identified using crystallography.

However, attempts to crystallize the PTEN dimer failed. To compensate, the researchers used a different methodology called small-angle X-ray scattering, which gains information by scattering X-rays through a solution containing the protein. Computer modeling was then performed to establish the dimer’s structure.

Findings indicated that in the PTEN dimers, the C-terminal tails of the 2 proteins may bind the protein bodies together, making them more stable. As a result, they can more efficiently interact with the cell membrane, regulate cell growth, and suppress tumor formation.

Thanks to this breakthrough study, scientists will now be able to evaluate the atomic-scale mechanisms of tumor growth perpetuated by PTEN mutations. This finding could offer an alternative route to cancer treatment in the future with further investigation.