β-catenin nuclear translocation induced by HIF-1α overexpression leads to the radioresistance of prostate cancer

Simple item page
dc.contributor.authorLuo, YONG
dc.contributor.authorLi, MINGCHUAN
dc.contributor.authorZuo, XUEMEI
dc.contributor.authorBASOURAKOS, SPYRIDON P.
dc.contributor.authorZhang, JIAO
dc.contributor.authorZhao, JIAHUI
dc.contributor.authorHan, Yili
dc.contributor.authorLin, YUNHUA
dc.contributor.authorWang, YONGXING
dc.contributor.authorJiang, YONGGUANG
dc.contributor.authorLan, Ling
dc.date.accessioned2020-04-03T18:36:53Z
dc.date.available2020-04-03T18:36:53Z
dc.date.issued2018-03-16
dc.description.abstractHypoxia-inducible factor-1α (HIF-1α) is known to play crucial roles in tumor radioresistance; however, the molecular mechanisms responsible for the promotion of tumor radioresistance by HIF-1α remain unclear. β-catenin is known to be involved in the metastatic potential of prostate cancer (PCa). In this study, to investigate the role of HIF-1α and β-catenin in the radioresistance of PCa, two PCa cell lines, LNCaP and C4-2B, were grouped as follows: Negative control (no treatment), HIF-1α overexpression group (transfected with HIF-1α overexpression plasmid) and β-catenin silenced group (transfected with HIF-1α plasmids and β-catenin-shRNA). Cell proliferation, cell cycle, cell invasion and radiosensitivity were examined under normal or hypoxic conditions. In addition, radiosensitivity was examined in two mouse PCa models (the LNCaP orthotopic BALB/c-nu mice model and the C4-2B subcutaneous SCID mice model). Our results revealed that in both the LNCaP and C4-2B cells, transfection with HIF-1α overexpression plasmid led to an enhanced β-catenin nuclear translocation, while β-catenin silencing inhibited β-catenin nuclear translocation. The enhanced β-catenin nuclear translocation induced by HIF-1α overexpression resulted in an enhanced cell proliferation and cell invasion, an altered cell cycle distribution, decreased apoptosis, and improved non-homologous end joining (NHEJ) repair under normal and irradiation conditions. Similar results were observed in the animal models. HIF-1α overexpression enhanced β-catenin nuclear translocation, which led to the activation of the β-catenin/NHEJ signaling pathway and increased cell proliferation, cell invasion and DNA repair. These results thus suggest that HIF-1α overexpression promotes the radioresistance of PCa cells.en_US
dc.identifier.doi10.3892/ijo.2018.4368
dc.identifier.urihttp://hdl.handle.net/10342/7942
dc.titleβ-catenin nuclear translocation induced by HIF-1α overexpression leads to the radioresistance of prostate canceren_US
dc.typeArticleen_US
ecu.journal.issue6en_US
ecu.journal.nameInternational Journal of Oncologyen_US
ecu.journal.pages1827-1840en_US
ecu.journal.volume52en_US

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
β-catenin_nuclear_translocatio.pdf
Size:
2.7 MB
Format:
Adobe Portable Document Format
Description:
Download

Collections

Open Access