New Lead For Breast Cancer Therapy
7 Jun, 2007 04:11 pm
Breast cancer is a deadly disease. This year over 170,000 new cases of breast cancer will be diagnosed in the United States. This year the number of new cases are approximately 125 per 100,000 for white women and approximately 116 per 100,000 for African American women. Similar trends are seen throughout the developed world. Over 40,000 women will die in the United States in 2007 due to failed therapeutic intervention with deaths related to the spread of cancer. The key genetic events governing the spread of breast cancer to the lungs and other tissues represents an ideal opportunity for intervention that may prolong the lives of patients affected with this disease.
These studies suggested that the AKT1 gene is required for the onset and growth of breast cancer caused by the ErbB2 oncogene. Furthermore, these studies suggested the AKT1 gene was important in the spread of breast cancer, which is a key cause of death in most women affected with this disease.
To examine the mechanism by which AKT1 induced the spread of breast cancer, we developed cell lines from the breast tumors caused by the ErbB2 oncogene. Cell lines were generated that either contained the AKT1 gene or were deleted of the AKT1 gene.
The cell lines expressing the ErbB2 oncogene, proliferated rapidly and were capable of migrating or spreading. In contrast, the breast cancer cell lines deleted of the AKT1 gene, failed to invade or migrate. In order to understand why the AKT1-deficient cells failed to move, we examined the factors secreted by the breast cancer cells. These studies identified a secreted factor produced by the breast cancer cells called CXCL16. This protein was secreted by the breast cancer cell and promoted its migration. The deletion of the AKT1 gene abolished the secretion of this factor and thereby blocked migration of the cells.
Together these studies suggest the AKT1 gene is an excellent candidate for breast cancer therapies, particularly breast cancer that has spread. The role of CXCL16 in promoting human breast cancer spread will be examined further. By identifying new therapeutic targets to block the spread of human breast cancer, we hope to prevent death from breast cancer. The development of drugs specifically targeted to AKT1 will require further evaluation.
Xiaoming Ju, et al, Akt1 governs breast cancer progression in vivo, Proceedings of the National Academy of Sciences, 25 April 2007
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