FIGURE 12.

Proposed model of cadmium-induced cell transformation and carcinogenesis. Chronic exposure of BEAS-2B cells to cadmium increases ROS, which induces cell transformation. After transformation, the transformed cells exhibit a property of autophagy dysfunction. Hyperactivation of p62 due to autophagy dysfunction activates positive feedback loop of Nrf2 and p62, which leads to up-regulation of antiapoptotic proteins (Bcl-2/Bcl-xL) and antioxidant enzymes (catalase, SOD1, and SOD2). Up-regulation of the antiapoptotic protein leads to apoptosis resistance. A low level of ROS due to up-regulation of the antioxidant enzymes causes less sensitivity to an apoptosis. Those factors contribute to cell proliferation and survival and carcinogenesis.