FAM134B'nin karaciğer kanserindeki rolü

The family with sequence similarity 134, member B (FAM134B) protein initially caught attention in our laboratory through demonstrating elevated levels possibly associated with senescent, cirrhotic, and mesenchymal-like states in hepatocellular carcinoma (HCC), and the aim of this thesis work was to identify the role of FAM134B in HCC. The work in this thesis initially demonstrated that the induction of endoplasmic reticulum (ER) stress in normal mice livers with 8 hours of tunicamycin treatment did not significantly alter the levels of FAM134B mRNA or protein. We then demonstrated that induction of ER stress in four HCC cell lines using several ER stress inducers such as thapsigargin, tunicamycin or DTT did not cause a significant increase in the levels of FAM134B mRNA or protein, with the exception of high dose DTT treatment of Snu449 cells which also demonstrated apoptosis. We also observed that FAM134B protein levels may be elevated during epithelial-to-mesenchymal transition (EMT) in PLC cells induced by TGF-ß treatment. Snu449 cells in which FAM134B was silenced demonstrated an altered morphology in cell culture, and appeared to lose their migratory capabilities. Most significantly though, FAM134B-silenced Snu449 cells demonstrated a dramatic loss of resistance to treatment with thapsigargin and adriamycin, which are both known to inhibit the calcium pumps on the ER. The knockdown cells also demonstrated loss of resistance to serum starvation, TGF-ß treatment, tunicamycin and alcohol treatment, but no significant difference was observed in resistance to 5-FU, camptothecin and hydrogen peroxide. These results implicated that FAM134B may play a role that is essential for survival under several forms of cytotoxic threat, especially those that disturb calcium homeostasis.