"We have greatly expanded our knowledge of the Nod1 pathway beyond its known role in response to infection," said Richard J. Ulevitch, Ph.D., professor at Scripps Research Department of Immunology. "These unexpected findings offer the first real evidence that this pathway may regulate tumour growth and suggest a potentially new mechanism for controlling this type of breast cancer."
In the study, researchers looked at a number of biological processes where Nod1-dependent apoptotic pathways were a critical component, including the regulation of tumour cell growth where the failure of malignant cells to undergo cell death led to tumourigenesis.
Cells derived from the human breast cancer epithelial cell line MCF-7 were used to induce tumour growth in severe combined immunodeficiency (SCID) mice. An over-expression of Nod1 in MCF-7 cells resulted in the inhibition of oestrogen-dependent tumour growth in the SCID mice and a reduction of oestrogen-induced proliferative responses in vitro. The tumours diminished rapidly in these mice, becoming virtually undetectable by the end of the experiment.
In MCF-7 cells where Nod1 was absent, the tumours flourished. In addition, there was an increased sensitivity to oestrogen-induced cell proliferation and a failure to undergo Nod1-dependent apoptosis in vitro.
Taking these initial findings, researchers implanted oestrogen pellets in the SCID mice to accelerate tumourigenesis. In those mice receiving Nod1 cell lines tumour growth did not occur even in the presence of oestrogen pellets, indicating that Nod1 acts as an effective cellular brake on oestrogen-dependent tumour growth.
MEDICA.de; Source: Scripps Research Institute