The expression of TFF1 is frequently down-regulated in human gastric cancer whereas its knockout leads to the development of gastric adenomas and carcinomas in mouse models. The molecular mechanisms underlying the TFF1 tumor suppressor functions remain unclear. In this study, we demonstrate, using colony formation assay and Annexin V staining, that reconstitution of TFF1 expression in gastric c...

The oncoproteins MDM2 and MDMX negatively regulate the activity and stability of the tumor suppressor protein p53 and are important molecular targets for anticancer therapy. Grafting four residues of p53 critical for MDM2/MDMX binding to the N-terminal alpha-helix of BmBKTx1, a scorpion toxin isolated from the venom of the Asian scorpion Buthus martensi Karsch, converts the miniature protein in...

p53 is the most frequent target for genetic alterations in a wide variety of human cancers. The product of the p53 tumor suppressor gene binds to DNA and activates transcription from promoters containing its consensus binding site. In the accompanying paper we have found that P53 tumor suppressor protein recognizes specifically a transcriptional element within the human H-ras protooncogene (Spa...

The development of cancer is a multistep process involving mutations in proto-oncogenes, tumor suppressor genes, and other genes which control cell proliferation, telomere stability, angiogenesis, and other complex traits. Despite this complexity, the cellular pathways controlled by the p53 tumor suppressor protein are compromised in most, if not all, cancers. In normal cells, p53 controls cell...

The traditional methods used to diagnose cancer and predict its course have been increasingly aided by molecular genetics. Unique, molecular genetic tumor markers are a consequence of the clonal expansion of cells which harbor one or more altered genes. Converging lines of evidence now firmly document that cancer is a type of genetic disease with genomic changes that are often somatically acqui...

Background:Non-Melanoma Skin Cancer (NMSC), the most prevalent types being Squamous Cell Carcinoma (SCC) and Basal Cell Carcinoma (BCC), is the most common type of malignancy in human beings. These neoplasms are more frequent in the elderly and fair skinned people and mainly occur on sun-exposed sites of the body. Ultraviolet B (UVB) has a wel...

The nuclear export protein chromosome maintenance region 1, found to be elevated in non-Hodgkin's lymphomas, controls localization of critical tumor suppressor proteins. Nuclear localization of tumor suppressor proteins is necessary for their cell surveillance function. However, their nuclear exclusion by chromosome maintenance region 1 renders them ineffective making this nuclear transporter a...

Understanding how the tumor suppressor p53 induces cell cycle arrest or apoptosis is critical for developing chemotherapeutic strategies. We have generated targeted transgenic reporter mice with which we can study p53 activity at specific promoters, and propose a model in which p53 protein conformation is key to target gene selection.