Gene family of potential tumor inhibitors identified

May 17 2006

Proteins from a newly discovered family of genes, LRIG, function as a retardant for a protein that is important to tumor cells. It is probably this mechanism that lends the gene family its inhibiting effect on cancer tumors.

This is shown in a dissertation by Jonas Nilsson at Umea University in Sweden, to be publicly defended on May 24.

Jonas Nilsson and his associates have identified a new family of genes, the leucin-rich and immunoglobulin-like (LRIG) family. They found that the first member of the family, LRIG1, shuts down the activity of the tumor protein ErbB1. LRIG1 introduces the ErbB1 protein to the protein degradation machinery, which in turn destroys the ErbB1 protein. In patients, they have also shown that expression of LRIG proteins is associated with increased survival rates in patients with malignant brain tumors.

Apace with the growth of our knowledge of oncology, new approaches have been developed for the treatment of tumors. For instance, treatments have been devised to seek out specific targets in the cancer cell, several of which are already in clinical use. One example is the treatment of breast cancer with Herceptin.

One type of target that these selective treatments seek out are receptors on the cell surface (receptors for growth factors). They are often hyperactive in tumors, which leads to increased resistance to chemo and radiation therapy, as well as increased tumor growth and metastasizing. Therefore, the idea is to shut down, or at least slow down, these hyperactive receptors as a way of defeating the tumor. The ErbB receptors belong to a class of cell-surface receptors, and when they are overly activated, which is often the case in tumors, they are associated with poor survival rates.

In his dissertation work, Jonas Nilsson looked for a naturally occurring retardant mechanism for ErbB receptors. He worked on a banana fruit fly protein, Kekkon-1, which serves to slow down the fly’s equivalent of the ErbB receptor. A similar protein was cloned for humans and then described and named leucin-rich and immunoglobulin-like protein 1 (LRIG1). The findings showed that LRIG1 belongs to a protein family of its own, with three family members, LRIG1, LRIG2 and LRIG3. Studies of LRIG1 showed that it binds to ErbB receptors and accelerates their degradation, thus slowing down their activity. LRIG2 and LRIG3 evince great similarities to LRIG1, which indicates that they may perform similar functions in the cell, but this has not yet been demonstrated. However, studies of brain tumors showed that the expression of LRIG proteins is associated with improved survival rates in patients. Further, it was shown that the expression of LRIG3 is an independent prognostic marker in malignant brain tumors.

In summary, by way of analogies to the banana fruit fly protein Kekkon-1, Jonas Nilsson’s dissertation identifies a new family of genes, confirms his theories that it functions as a retardant of the tumor protein ErbB1, and finally shows that the expression of LRIG proteins is associated with increased survival in patients with malignant brain tumors.