p53 Activation in Chronic Radiation-Treated Breast Cancer Cells

Abstract

Mammalian cells chronically exposed to ionizing radiation (IR) induce stress response with a tolerance to the subsequent cytotoxicity of IR. Although p53 is well documented in IR response, the signaling network causing p53 activation in chronic IR remains to be identified. Using breast carcinoma MCF؉FIR cells that showed a transient radioresistance after exposure chronically to fractionated IR (FIR), the present study shows that the basal DNA binding and transcriptional activity of p53 was elevated by FIR. p53-controlled luciferase activity was strikingly induced (ϳ7.9-fold) with little enhancement of p53/DNA binding activity (

miR-15b/16-2 Regulates Factors That Promote p53 Phosphorylation and Augments the DNA Damage Response following Radiation in the Lung

“…Both ATM and Chk1 have been reported to directly phosphorylate p53 on several N-terminal sites (30). It has also been reported that IR activates p53 by inducing phosphorylation at the N-and C-terminal phosphorylation sites as well as direct down-regulation of MDM2 expression (31). We observed a time-dependent induction in phosphorylated p53 and decrease in MDM2 levels following IR in miR-15b/ 16-2 cells.…”

Differential gene expression profiles of radioresistant pancreatic cancer cell lines established by fractionated irradiation

“…Up-regulated genes were associated with growth factors, cell-cycle check points, intracellular signaling pathways and angiogenesis stimulation, whereas down-regulated genes were associated with apoptosis, retinoid esterification and electron transport. Previous reports concerning breast, esophageal and uterine cervical cancer also indicated that growth factors and intracellular signaling pathways were up-regulated while apoptosis-related genes were down-regulated in the radioresistant cancer or cancer cell lines (13)(14)(15)(16)). In the current study, some of these genes were previously known to be associated with responsiveness to radiation, such as caspase 8 and MAPKAPK2, but others were novel.…”

“…The advent of microarray gene expression technology permits simultaneous analysis of the expression levels of thousands of genes (10-12). Therefore, a study on molecular genetic events related to radiosensitivity can be conducted (13)(14)(15)(16). This research may also lead to identification of gene regulatory pathways that result in development of cell resistance to therapeutic procedures.…”

“…This research may also lead to identification of gene regulatory pathways that result in development of cell resistance to therapeutic procedures. To date, differential gene expression profiles of radioresistant cancer and cancer cell lines including breast cancer, esophageal cancer and uterine cervical cancer have been reported (13)(14)(15)(16). However, to the authors' knowledge, there has been no information regarding the global gene analyses of radioresistant pancreatic cancer or cancer cell lines.…”

Cytogenetic effects and possibilities of their transgenerational transfer in the generations of persons living in radionuclide polluted areas after the Chernobyl accident

“…Можно предполагать, что при длительно персистирующей радиационной нагрузке данные от-личия связаны с подавлением апоптотической гибели лимфоцитов. Предположение о наличии угнетающе-го действия хронического облучения на способность клеток к гибели по механизму апоптоза было выска-зано некоторыми авторами, сообщавшими об угне-тении р53-зависимого апоптоза под влиянием хрони-ческого облучения [24].…”