Expression of NF-κB p65 phosphorylated at serine-536 in rectal cancer with or without preoperative radiotherapy
نویسندگان
چکیده
BACKGROUND In the present study, we investigated NF-κB p65 phosphorylated at Serine-536 (phosphor-Ser536-p65) in rectal cancer and its relationship to preoperative radiotherapy (RT), clinicopathological variables and biological factors. PATIENTS AND METHODS Expression of phosphor-Ser536-p65 was examined by using immunohistochemistry in 141 primary rectal cancers, 149 normal mucosa specimens and 48 metastases in the lymph nodes, from rectal cancer patients who participated in a Swedish clinical trial of preoperative RT. RESULTS The expression of phosphor-Ser536-p65 in the cytoplasm increased from normal mucosa to primary tumour (p<0.0001, for both the group that did and the group that did not received RT). The expression did not further increase from primary tumour to metastasis in either group (p>0.05). Expression of phosphor-Ser536-p65 was positively related to, or tended to be related to, the expression of tumour endothelium marker 1 (TEM1, p=0.02), FXYD-3 (p=0.001), phosphatase of regenerating liver (PRL, p=0.02), p73 (p=0.048) and meningioma associated protein (MAC30, p=0.05) in the group that received RT but there were no such relationships in the group that did not received RT (p>0.05). The expression of phosphor-Ser536-p65 was not related to clinicopathological factors including survival (p>0.05). CONCLUSIONS The increased expression of phosphor-Ser536-p65 may be involved in rectal cancer development. After RT, phosphor-Ser536-p65 seems to be positively related to the biological factors, which associated with more malignant features of tumours. However, phosphor-Ser536-p65 was not directly related to the response of RT based on recurrence and survival.
منابع مشابه
VGB3 Induces Apoptosis by Inhibiting Phosphorylation of NF-κB p65 at Serine 536 in the Human Umbilical Vein Endothelial Cells
Background and objectives: Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibition results in an increase in apoptosis. It has been demonstrated that NF-κB subunit p65 phosphorylation at the IκB kinase phosphorylation site serine 536 (Ser536) is essential for the NF-κB nuclear translocation and activation. Therefore, NF-κB can be downregulated by suppressing its phosph...
متن کاملCyclin-Dependent Kinase 6 Phosphorylates NF-κB P65 at Serine 536 and Contributes to the Regulation of Inflammatory Gene Expression
Nuclear factor kappa-B (NF-κB) activates multiple genes with overlapping roles in cell proliferation, inflammation and cancer. Using an unbiased approach we identified human CDK6 as a novel kinase phosphorylating NF-κB p65 at serine 536. Purified and reconstituted CDK6/cyclin complexes phosphorylated p65 in vitro and in transfected cells. The physiological role of CDK6 for basal as well as cyto...
متن کاملSpecification of the NF-κB transcriptional response by p65 phosphorylation and TNF-induced nuclear translocation of IKKε
Here we investigated the regulation of NF-κB activity by post-translational modifications upon reconstitution of NF-κB p65-deficient cells with the wild-type protein or phosphorylation-defect mutants. Analysis of NF-κB target gene expression showed that p65 phosphorylations alone or in combination function to direct transcription in a highly target gene-specific fashion, a finding discussed her...
متن کاملTraf1 induction and protection from tumor necrosis factor by nuclear factor-kappaB p65 is independent of serine 536 phosphorylation.
Abnormal nuclear factor-kappaB (NF-kappaB) signaling has been attributed to the initiation and progression of cancer. Posttranslational modification of p65 facilitates optimal NF-kappaB signaling after activation. Here, we show that the phosphorylation of serine 536 was required for p65-mediated transcription and I kappa B alpha expression in fibroblasts. Furthermore, tumor necrosis factor (TNF...
متن کاملThe effects of adenosine injection after of brain ischemia reperfusion injury on gene expression of NF-kB/p65 and activity level of ROS in male Wistar rats
Background: Unit of p65 is one of the subunits of NF-κB and its phosphorylation by stress oxidative causes activation of NF-κB. The aim of present study was to investigate the effects of adenosine injection after brain ischemia reperfusion injury on gene expression of NF-κB /p65 and Reactive Oxygen Species (ROS) in hippocampus tissue of male wistar rats. Methods: 40 male wistar rats were rando...
متن کامل