| First Author | Yoshida T | Year | 2013 |
| Journal | Lab Invest | Volume | 93 |
| Issue | 11 | Pages | 1184-93 |
| PubMed ID | 24042437 | Mgi Jnum | J:202472 |
| Mgi Id | MGI:5519161 | Doi | 10.1038/labinvest.2013.111 |
| Citation | Yoshida T, et al. (2013) Transcriptional upregulation of HIF-1alpha by NF-kappaB/p65 and its associations with beta-catenin/p300 complexes in endometrial carcinoma cells. Lab Invest 93(11):1184-93 |
| abstractText | The hypoxia-inducible factor (HIF)-1alpha, which has a major role in cell adaptation to hypoxia, is mainly regulated at post-translational levels. Recently, HIF-1alpha mRNA was also shown to be upregulated by several signal pathways under normoxic conditions. Here we focused on relationships of HIF-1alpha with NF-kappaB and beta-catenin signaling in endometrial carcinomas (Em Cas). Long-term exposure of Ishikawa cells to cobalt chloride (CoCl2), which is known to mimic the effect of hypoxia, caused a decrease in the growth, along with increased HIF-1alpha protein but not mRNA expression. In contrast, short-term exposure resulted in a rapid and transient increase in HIF-1alpha mRNA expression along with stabilization of nuclear NF-kappaB/p65 (p65). Transfection of p65 increased HIF-1alpha expression through activation of the promoter, whereas overexpression of HIF-1alpha also activated NF-kappaB-dependent transcription, indicating the existence of a positive feedback loop. In addition, HIF-1alpha was indirectly associated with nuclear beta-catenin through interactions with p300, leading to slight enhancement of both HIF-1alpha- and beta-catenin-mediated transcriptional activity. In clinical samples, biphasic upregulation of HIF-1alpha expression was observed in normal endometrial glandular components during the menstrual cycle, with the labeling indices showing significantly higher values in the early secretory stage. Significantly higher values for phosphorylated p65 and nuclear beta-catenin were also observed in HIF-1alpha-positive than -negative lesions of Em Cas, in contrast to significantly lower Ki-67 status. These data therefore suggest that transcriptional associations with HIF-1alpha and NF-kappaB, as well as beta-catenin/p300 complexes, may contribute to modulation of changes in tumor cell kinetics in response to a hypoxic condition in Em Cas. |
