Abstract 1426: Cyclooxygenase-2 (COX-2) utilizes Jun N-terminal kinases to induce invasion but not tamoxifen resistance in MCF-7 breast cancer cells

Abstract

Abstract Elevated Cyclooxygenase-2 (COX-2) expression in breast tumors had been associated with a lower survival rate in patients with Estrogen Receptor α (ERα)-positive tumors. We propose that COX-2 reduces survival rate in breast cancer patients with ERα-positive tumors because COX-2 decreases tamoxifen sensitivity and increases invasive activity of breast cancer cells. We demonstrated that transfection of the COX-2 gene in the tamoxifen-sensitive, ERα-positive MCF-7 breast cancer cell line decreased the cells’ sensitivity to tamoxifen by about 5-fold, and increased their invasive activity by about 3-fold. Furthermore, we demonstrated that COX-2 utilizes PGE2 to activate Protein Kinase C (PKC) to induce these tumorigeneic effects. However, which downstream factors are recruited by the COX-2/PGE2/PKC pathway to induce tamoxifen resistance and breast cancer cell invasion are not known. Here we report that COX-2 increases the phosphorylation of Jun N-terminal kinase (JNK), but not that of extracellular signal regulated kinases (ERK1,2), p38 mitogen activated protein kinase, or Akt. Inhibition of JNK by a chemical inhibitor or siRNA led to decreased COX-2-mediated invasion. Yet, JNK inhibition did not affect COX-2-mediated tamoxifen resistance. We propose that JNK is a promising target to block invasion in patients whose tumors are ERα-positive and present high levels of COX-2. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 1426. doi:10.1158/1538-7445.AM2011-1426