George G Chen, Presenter: Nothing to Disclose

ZM Liu, Abstract Co-Author: Nothing to Disclose

AC Vlantis, Abstract Co-Author: Nothing to Disclose

BCH Leung, Abstract Co-Author: Nothing to Disclose

CA van Hasselt, Abstract Co-Author: Nothing to Disclose

Cell death is an important index to justify the efficiency of chemo- or radio-therapy of thyroid cancer. The role of heme oxygenase-1 (HO-1) and p21 in the cell death of thyroid cancer is unknown. The aim of the study is thus to reveal how HO-1 and p21 participate thyroid cancer cell death.

The study was performed using a thyroid papillary carcinoma cell line (KAT5 cells) and cell death was evaluated by various assays.

HO-1 could be significantly induced by hemin and cadmium. In addition to inducing HO-1, hemin and cadmium also caused a rise in the levels of p21, a cyclin-dependent kinase inhibitor. Cells with increased levels of HO-1 and p21 were more resistant to cell death stimuli than cells with normal levels and the apoptosis was the main form of cell death in the present study. The induced levels of HO-1 and p21 were significantly reduced by p38 mitogen-activated protein kinase (p38 MAPK) and extracellular-regulated kinase (ERK) inhibitors. More importantly, KAT5 cells regained their sensitivity to apoptotic stimuli after they were treated with these kinase inhibitors, indicating that p38 MAPK and ERK are required for the resistance to apoptosis conferred by HO-1. Furthermore, we demonstrated that increased levels of HO-1 and p21 expression are associated with an increase in the activity of NF-kappaB and that inhibiting NF-kappaB leads to a block in the induction of HO-1 and p21.

This study reveals that an increase in the level of HO-1 markedly reduces the sensitivity of papillary thyroid carcinoma cells to apoptotic stimuli. The HO-1 pathway of apoptosis resistance is associated with an increase in the levels of p21, involves a p38 MAPK and ERK-mediated mechanism and can be suppressed by inhibiting NF-kappaB.

Chen, G, Liu, Z, Vlantis, A, Leung, B, van Hasselt, C, Role of Heme Oxygenase-1 and p21 in Protection of Thyroid Cancer Cell Death.  Radiological Society of North America 2004 Scientific Assembly and Annual Meeting, November 28 - December 3, 2004 ,Chicago IL. http://archive.rsna.org/2004/4407684.html