Animal and Cell Line Studies

COX-2 protein has been immunolocalised to malignant epithelial cells within breast tumours induced in a rat model by various carcinogens (52, 53). Transgenic mice overexpressing breast-targeted oncogenes such as Wnt-1 develop mammary tumours which contain significant amounts of COX-2 (54).

A recent study used transgenic mice to examine the effects of COX-2 overexpression in the breast (55). Invasive breast tumours occur with high frequency after successive rounds of pregnancy in these mice, and are prone to metastasis. The study revealed only pregnancy or lactation resulted in exaggerated induction of COX-2, and tumorogenesis occurred only in multiparous mice. A low level of COX-2 expression occurred in virgin mice, which displayed precocious mammary gland development, but no tumour formation. This suggests a high level of COX-2 expression is required to allow carcinoma development, probably in addition to other sustained insults to the genome. Although the effects of targeted disruption of COX-2 genes upon mammary carcinogenesis has not yet been studied, it is informative that in a rodent colorectal cancer model, this strategy leads to a reduction in intestinal adenoma incidence of 86% in COX-2 null mice, and 66% in heterozygous mice (56).

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