Search

Simple Summary Tumor suppressor genes are critical in the control of many biological functions. They can be classified based on their roles in proliferation, cell-cycle progression, DNA repair/damage, and crucial signaling functions, including apoptosis, autophagy, and necrosis. The absence of functional tumor suppressor genes entails a higher risk of dysfunction of cell growth, differentiation, cell death, and cancer development. Loss of function or mutations of such genes has been identified in many types of cancer, such as breast, bladder, colorectal, head and neck, lung, ovarian, uterine, and pancreatic cancers. Familial cancer syndromes, such as Li–Fraumeni syndrome, are associated with loss of TP53 function. Extensive studies have been carried out to clarify the roles of the products of these genes, as well as their mechanistic link to cancers, to identify novel targets for specific cancer types. Here, we introduce the roles of tumor suppressor gene products in pancreatic cancer development and its therapeutics for tumorigenesis prevention. Abstract The high mortality of pancreatic cancer is attributed to the insidious progression of this disease, which results in a delayed diagnosis and advanced disease stage at diagnosis. More than 35% of patients with pancreatic cancer are in stage III, whereas 50% are in stage IV at diagnosis. Thus, understanding the aggressive features of pancreatic cancer will contribute to the resolution of problems, such as its early recurrence, metastasis, and resistance to chemotherapy and radiotherapy. Therefore, new therapeutic strategies targeting tumor suppressor gene products may help prevent the progression of pancreatic cancer. In this review, we discuss several recent clinical trials of pancreatic cancer and recent studies reporting safe and effective treatment modalities for patients with advanced pancreatic cancer.

We report here that the Jun dimerization protein 2 (JDP2) plays a critical role as a cofactor for the transcription factors nuclear factor-erythroid 2-related factor 2 (Nrf2) and MafK in the regulation of the antioxidants and production of reactive oxygen species (ROS). JDP2 associates with Nrf2 and MafK (Nrf2-MafK) to increase the transcription of antioxidant response element-dependent genes. Oxidative-stress-inducing reagent led to an increase in the intracellular accumulation of ROS and cell proliferation in Jdp2 knock-out mouse embryonic fibroblasts. In Jdp2-Cre mice mated with reporter mice, the expression of JDP2 was restricted to granule cells in the brain cerebellum. The induced pluripotent stem cells (iPSC)-like cells were generated from DAOY medulloblastoma cell by introduction of JDP2, and the defined factor OCT4. iPSC-like cells expressed stem cell-like characteristics including alkaline phosphatase activity and some stem cell markers. However, such iPSC-like cells also proliferated rapidly, became neoplastic, and potentiated cell malignancy at a later stage in SCID mice. This study suggests that medulloblastoma cells can be reprogrammed successfully by JDP2 and OCT4 to become iPSC-like cells. These cells will be helpful for studying the generation of cancer stem cells and ROS homeostasis.