p73, a potential tumor suppressor, is a p53 homologue. Transient over expression of p73 in cells can induce apoptosis and p21, a cellular p53 target gene primarily responsible for p53-dependent cell cycle arrest. To further characterize the role of p73 in tumor suppression, we established several groups of cell lines that inducibly express p73 under a tetracycline-regulated promoter. By using t...

Alteration in the p53 gene leads to uncontrolled cell proliferation and when these changes accumulate, it may result in carcinogenesis. A plethora of proteins have been reported that bind to the various regions of p53 in order to regulate the specificity of its activity. In the present study, our aim was to understand these connections so we have analyzed the networking role of p53 gene using ‘...

The clinically used antitumor agent mitomycin C (MC) alkylates DNA upon reductive activation, forming six covalent DNA adducts in this process. This paper focuses on differential biological effects of individual adducts in various mammalian cell cultures, observed in the authors' laboratories. Evidence is reviewed that various adducts are capable of inducing different cell death pathways in can...

Most studies of IR effects on neural cells and tissues in the brain are still focused on loss of neural stem cells. On the other hand, the effects of IR on neuronal differentiation and its implication in IR-induced brain damage are not well defined. To investigate the effects of IR on C17.2 mouse neural stem-like cells and mouse primary neural stem cells, neurite outgrowth and expression of neu...

Colorectal cancer (CRC) is one of the most common malignancies globally, and morbidity mortality rates associated with it are among highest around world. Not even great advances in colorectal diagnosis treatment technologies have been able to increase 5-year survival rate this disease. Recidivation metastasis main causes death CRC, although underlying mechanism remains unknown. Long non-coding ...

Microsatellite instability (MSI) is present in about 15% of colorectal cancers and plays critical roles in the development and progression of these cancers. The goal of this study is to determine the global effect of microsatellite instability on the signaling pathways and network in colon cancer cells. We profiled the expression and phosphorylation of 110 proteins in six colon cancer cell line...

Malignant glioma is the most common brain tumor in adults and is associated with a very poor prognosis. Mutations in the p53 tumor suppressor gene are frequently detected in gliomas. p53 is well-known for its ability to induce cell cycle arrest, apoptosis, senescence, or differentiation following cellular stress. That the guardian of the genome also controls stem cell self-renewal and suppresse...

Background: Loss of p53 activity is important for tumor initiation and progression. While approximately 50% tumors lose through inactivating mutations in TP53, harness other mechanisms to inactivate p53, including MDM2, an E3 ligase that targets proteasomal degradation. Milademetan MDM2 inhibitor currently being evaluated clinical trials. The MAPK pathway commonly activated by the RTK-RAS-RAF-M...

Protein tyrosine phosphatase 1B (PTP1B) is involved in multiple signaling pathways by down-regulating several tyrosine kinases. For example, gene-targeting studies in mice have established PTP1B as a critical physiologic regulator of metabolism by attenuating insulin signaling. PTP1B is an important target for the treatment of diabetes, because the PTP1B null mice are resistant to diet-induced ...

Precise regulation of signal transduction pathways is crucial for normal animal development and for maintaining cellular and tissue homeostasis in adults. The Wnt/Frizzled-mediated signaling includes canonical and non-canonical signal transduction pathways. Upregulation or downregulation of the canonical Wnt-signaling (or the Wnt/β-Catenin signal transduction) leads to a variety of human diseas...