Upregulation of genes for C-reactive protein and related pentraxin/complement proteins in photodynamic therapy-treated human tumor cells: Enrolment of PI3K/Akt and AP-1

Abstract

Treatment of mouse tumors by photodynamic therapy (PDT) was reported to trigger the production of serum amyloid P component (SAP), a prototypic acute phase reactant in the mouse, that occurs in the targeted tumor as well as distant sites dominated by host's liver. It was also shown that the SAP gene becomes upregulated and protein produced in mouse tumor cells treated by PDT in vitro. Present study revealed that, in addition to SAP, increased expression of genes encoding related pentraxin and complement proteins, including PTX3, C1q and ficolin B, can be found in mouse LLC tumor cells treated by PDT. Since in humans C-reactive protein (CRP) is more important acute phase reactant than SAP, the expression of gene encoding this pentraxin protein was examined in human lung tumor A549 cells treated by PDT. The results demonstrated a PDT dose-dependent upregulation of CRP gene, as well as of PTX3 and ficolin 1 genes in these cells. Investigation into the signal transduction process underlying PDT-induced human CRP gene upregulation using specific inhibitors of critical signaling elements revealed critical role played by PI3K/Akt pathway. Downstream DNA transcription factor largely responsible for this increased CRP gene expression is AP-1 with possible cooperation of HIF-1. It was suggested that cells sensing to have sustained a mortal injury from PDT can turn on molecular programs ensuring that the disposal of their corpses (facilitated by CRP and related pentraxin and complement components) is swift and efficient.