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Breast Cancer Res. 2009;11(2):R21. doi: 10.1186/bcr2246. Epub 2009 Apr 24.

Interleukin-1beta and fibroblast growth factor receptor 1 cooperate to induce cyclooxygenase-2 during early mammary tumourigenesis.

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Microbiology, Immunology and Cancer Biology Graduate Program, University of Minnesota, Minneapolis, MN 55455, USA.



Inflammation within the tumour microenvironment correlates with increased invasiveness and poor prognosis in many types of cancer, including breast cancer. We have previously demonstrated that activation of a mouse mammary tumour virus (MMTV)-driven inducible fibroblast growth factor receptor 1 (iFGFR1) transgene in mammary epithelial cells results in an inflammatory response characterised by induction of inflammatory genes in the mammary gland. Specifically, we have observed increased levels of IL-1beta expression in the mammary gland following activation of iFGFR1 and have used the iFGFR1 model to elucidate the function of IL-1beta in promoting iFGFR1-induced mammary lesions.


To determine the functional consequences of IL-1beta induction during FGFR1-induced mammary tumourigenesis, the effects of IL-1beta inhibition on the formation of epithelial hyperplasias were examined using the MMTV-iFGFR1 transgenic mouse model. Further studies used a combination of the HC-11 mammary epithelial cell line that stably expresses iFGFR1 and the MMTV-iFGFR1 transgenic mice to further define the mechanisms of IL-1beta function.


Inhibition of IL-1beta activity in vivo resulted in reduced iFGFR1-induced epithelial proliferation and formation of hyperplastic structures. Further studies demonstrated that treatment of mammary epithelial cells with IL-1beta-induced expression of cyclooxygenase (Cox)-2 both in vitro and in vivo. Finally, inhibition of Cox-2 prior to activation of iFGFR1 in the transgenic mice also resulted in decreased iFGFR1-induced formation of hyperplastic structures.


The results from these studies indicate that targeting the inflammatory cytokine IL-1beta partially inhibits iFGFR1-induced formation of early-stage mammary lesions, in part through induction of Cox-2. These findings demonstrate that activation of a growth factor receptor in mammary epithelial cells results in increased expression of inflammatory mediators, which cooperate to promote the initiation of hyperplastic lesions in the mammary gland.

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