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Turning a Cancer Cell to a Normal Cell in the Body

Cathy Shachaf
Stanford University
November 2002

My research is in the field of Medical Oncology where I study how a cancer gene causes cancer in the body. We are able to activate a cancer gene in mice to cause cancer and when we inactivate the cancer gene the mice are cured. Studying this process might lead to a novel approach in curing cancer.

In my research I study at what level a cancer gene can turn any cell in any organ in the body into cancer and at what level the gene will not have any pathological effect on the cell.

Using a mouse system where we have incorporated one of the most potent cancer causing gene in such a way in the mouse, that we can control where and when we express the cancer gene. By feeding the mice with a chemical we cause the gene to be silent and when we stop feeding the chemical the cancer gene is expressed. In this system when the gene is activated the mice get cancer. Surprisingly when the cancer gene is inactivated in the mice that have cancer, the mice get cured from cancer. In humans in normal pathologic situations it is hard to treat people by repairing the initial genetic cause for the disease. Therefore we are trying to look at the indirect effects of inactivation of the cancer gene. By looking at secondary effects of inactivation of cancer in different tissues we might be able define a common mechanism of transformation from cancer to normal that will be usful for the treatment of cancer.

In the initial experiment we have isolated the cancer cells and grow them in culture outside the context of the body. I am able to adjust the levels of the cancer gene in the cells growing in culture by adding different levels of chemical to the culture media. Using a technique where we can measure the levels of specific proteins in a sample, we have defined the level of the cancer protein in the cell that is sufficient to cause the cell to be cancerous or normal. If the protein is expressed above this level the cell will behave as a cancer cell. Likewise if the protein is expressed below this level the cell will behave as a normal cell.

Using the same technique I have induced cancer in the mouse and I treat them with different levels of the chemical. The different levels of the chemical will cause different levels of expression of the cancer gene. In mice where the expression of the gene is inhibited the mice are cured. Low levels of the chemical have no effect on the expression of the gene and the mice become even sicker. I am hoping to find a level where the level of expression of the gene will have no affect on the cancer.

I am trying to unravel the genetic pathway that is involved in turning the cancer cell into a normal cell. To do this I am using techniques that identify genes and the level of these genes that are expressed in the cell when it behaves like a normal cell and when it behaves like a cancer cell. Comparison of the gene patterns in both cases might highlight s group of genes that play an important function in turning a cancer cell into a normal cell.

Once I have defined the genes and the levels of the genes involved in the mechanism of turning a cancer cell into a normal cell I will look for a way to inhibit the group of genes using a pharmacological or biological approach. In the pharmacological approach I will use specific known inhibitors for specific gene products. Where this is not known or available I will use a biological approach using gene therapy techniques to inhibit the activity of specific genes.