MDM2 binds the p53 tumor suppressor protein with high affinity and negatively modulates its transcriptional activity and stability. Overexpression of MDM2, found in many human tumors, effectively impairs p53 function. Inhibition of MDM2-p53 interaction can stabilize p53 and may offer a novel strategy for cancer therapy. Here, we identify potent and selective small-molecule antagonists of MDM2 a...

abstract introduction. p53 has been known as a tumor suppressor gene and also ki-67 is a cell cycle regulator. the aim of present study was to investigate p53 and ki-67 protein expression in the epithelial lining of odontogenic cysts and its correlation with their biologic behavior and the degree of inflammation within the cyst wall. methods. p53 and ki-67 immunoreactivity in 58 odontogenic cys...

introduction: the tumor suppressor p53 protein can induce apoptosis in some cellular contexts. among the apoptosis-inducing genes, p53 has received the most attention for cancer gene therapy. in this study, the role of dendrosome and lipofectin mediated normal cdna of tp53 into molt-4, ccrf-cem(t-iymphoma) and k562 cell lines was assessed. material and methods: at first, ccrf-cem, mol t-4 and k...

Many studies have been focused on cytogenetic and molecular genetic defects in brain tumors; therefore the role of ATM as a tumor suppressor gene in these tumors is poorly considered. In this study mutation analysis of exon 19 and 39 of ATM gene and P53 accumulation were investigated by PCR-SSCP, sequencing, and flow cytometry . Four polymorphisms including D1853N, IVS 38-8 T?C, F858L, P872T we...

KAI1 is a tumor metastasis suppressor gene that is capable of inhibiting the metastatic process in animals. The expression of the KAI1 gene also is found to be down-regulated during the tumor progression of prostate, breast, lung, bladder, and pancreatic cancers in humans, and this down-regulation appears to be at or posttranscription level. We have found that the tumor suppressor gene p53 can ...

Iron excess is closely associated with tumorigenesis in multiple types of human cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has emerged as a major strategy for chemotherapy, but it exerts tumor suppression only on select human malignancies. Here, we report that the tumor suppressor protein p53 is downregulated during iron excess. Strikingly, the iron polyporphyri...

The Ras oncoprotein is a key driver of cancer. However, Ras also provokes senescence, which serves as a major barrier to Ras-driven transformation. Ras senescence pathways remain poorly characterized. NORE1A is a novel Ras effector that serves as a tumor suppressor. It is frequently inactivated in tumors. We show that NORE1A is a powerful Ras senescence effector and that down-regulation of NORE...

Background: Cervical cancer is the third most common cancer in women throughout the world. The human papillomavirus (HPV) E6 viral protein plays an essential role in proteasomal degradation of the cancer suppressant protein p53. As a result, p53 negative regulation and apoptosis relevant activities are abrogated, facilitating development of cervical cancer. Methods: A mathematical model of E6-p...

Little or no data exist concerning the inactivation of tumor suppressor genes in intraductal lesions surrounding invasive ductal pancreatic carcinomas. Using a novel improved primer extension and preamplification polymerase chain reaction, we analyzed microdissected paraffin-embedded specimens of pancreatic carcinoma (n = 29) and their corresponding pancreatic intraductal lesions (PIL, n = 331)...

Over half of all human cancers, of a wide variety of types, sustain mutations in the p53 tumor suppressor gene. Although p53 limits tumorigenesis through the induction of apoptosis or cell cycle arrest, its molecular mechanism of action in tumor suppression has been elusive. The best-characterized p53 activity in vitro is as a transcriptional activator, but the identification of numerous additi...