Reduced tumor growth in mice lacking Egr‐1

Abstract

Early growth response-1 (Egr-1) is an immediate-early transcription factor inducible in the vasculature in response to injury, shear stress, and other stimuli. We have shown that mice lacking Egr-1 have a profound deficit in the ability to recover from femoral artery ligation, suggesting a role in neovascularization. Tumors are known to be able to signal the surrounding tissue to provide an increased blood supply to meet the needs of the growing tumor. We hypothesized that Egr-1 knockout mice would have a reduced capacity to respond to such signals. We injected 106 Lewis Lung Carcinoma (LLC) cells subcutaneously in the flank of wildtype (WT) and Egr-1 knockout (KO) mice. Tumors were excised and weighed at two weeks. The average mass of tumors from WT mice was 479 ± 128 mg, while those from KOs was 189 ± 57 mg (n=6 in both groups, P=0.002). The slower tumor growth in KO mice was associated with a 5.8-fold increase in the tumor tissue levels of CXCL9 (also known as MIG), a chemokine that is chemotactic for T-cells and natural killers and is known to have anti-angiogenic properties. In conclusion, this study shows that LLC tumor development is significantly suppressed in Egr-1 KO mice, suggesting an important role for Egr-1 in the regulation of tumor growth.