ERBB2 and breast cancer: Wang et al. demonstrated the ability of nuclear HER2 to transactivate COX-2 in colon cancer cells by binding to its promoter region, thus upregulating expression of COX-2 [33], while HER2 has also be shown to up-regulate COX-2 expression through Ras → Raf → MAPK → AP1 mechanisms in breast cancer cells [34].