Brain Cadherin in Human Breast Carcinoma

PUBLIC ABSTRACT

I am a research scientist committed to studying breast cancer to improve therapies and ultimately find cures. Breast cancer is the most common cancer in women in the Western world and about 1 in 10 women will develop the disease in their lifetime. This project proposal focuses on a gene, Br-cadherin, for which we have new evidence that it may be involved in cancer development and progression.

Cadherins are a family of related proteins located on the surface of cells. They are involved in maintaining the shape of the cell by interacting with structural molecules inside the cell, and they are also a component of the anchoring between cells so that they form tissues. Cadherins also function to convey signals from outside the cell to pathways inside the cell that affect the cell's behavior. Although several other cadherin proteins have been shown to be involved in breast cancer, the specific cadherin molecule we are focusing on, Br-cadherin, has not yet been studied in relation to any type of cancer. What is known is that Br-cadherin is not found in normal, healthy breast tissue, and hence does not seem to have any function in the non-cancerous breast.

Breast cancer arises when the activity of certain genes are altered so that a cell grows and divides uncontrollably; however, the exact combination of genes that are required for a cell to become cancerous varies, and the process is incompletely understood. Breast cancers with alterations in a similar set of genes are thought to be more related and are usually referred to as belonging to a subgroup. Using state-of-the-art molecular profiling technologies, we have discovered that Br-cadherin is found at high levels in a particular subgroup of breast cancer patients where the treatment is usually unsuccessful and the patients have a worse disease outcome. This subgroup represents about 30% of all breast cancers. We have also found evidence that the Br-cadherin molecule is more abundant in tumors that have spread to distant organs compared to tumors that have not spread, indicating that it may be involved in this process, which is the major cause of cancer patient death. Our research project aims to study Br-cadherin and investigate its role in breast cancer.

We will first determine the frequency of Br-cadherin overexpression in a large series of breast cancers and test whether patients with high levels have a worse outcome. In addition, using cells both from breast cancers and from non-cancerous normal breast tissues that can be grown in the laboratory, we will investigate how an increased or decreased abundance of Br-cadherin alters the cell's ability to replicate, change shape, and migrate, characteristics that are directly related to the aggressiveness of a cancer.

We believe that the results of this project may be important for the diagnosis and treatment of breast cancer patients. For example, Br-cadherin abundance in a tumor may be a useful marker of an aggressive cancer that would warrant prescribing a more forceful therapy. Moreover, Br-cadherin could be a good target to develop medical drugs toward, especially since it is found on the surface of the cell, which would allow the drug to meet its target more easily.