Role of TGF-β1/SMAD signaling cascade in the regulation of cyclooxygenase-2 expression in human breast cancer cells

Abstract

The expression of the SMAD2, SMAD4, SMAD7, and СOX-2 genes and the levels of Smad4, phosphorylated Smad2, and Smad7 proteins were analyzed in the human breast cancer (BC) cell lines MCF-7, BT-474, and ZR-75-1. The SMAD2 and SMAD4 genes were found to suppress COX-2 gene expression in the estrogen receptor-positive BC cells and to be linked to their metastatic potential. Smad4 and Smad2 apparently suppress COX-2 mRNA and protein synthesis and Smad7 is their antagonist and stimulates COX-2 formation. Smad2, Smad4, Smad7 proteins may be regarded as new potential targets for targeted BC therapy.

Keywords

• breast cancer
• cyclooxygenase-2 (cox-2)
• tgf-β1/smad signaling pathway
• smad2
• smad4
• and smad7 genes
• smad4
• smad2
• and smad7 proteins
• phosphorylated smad2
• inhibitors of cox-2
• pge2
• human breast cancer cell lines mcf-7
• bt-474
• and zr- 75-1
• targets f