An enhancement in the sensitivity of refractory pancreatic cancer cells to anti-tumor drugs through the functional regulation of RUNX2.

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08412
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: OZAKI TOSHINORI 千葉県がんセンター(研究所), 発がん研究グループ DNA損傷シグナル研究室, 室長 (40260252)
• Co-Investigator(Kenkyū-buntansha): 永瀬 浩喜 千葉県がんセンター(研究所), がん遺伝創薬研究室, 研究所長 (90322073)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: RUNX2 / 膵臓がん / 抗がん剤感受性

Outline of Final Research Achievements

RUNX2 which belongs to RUNX transcription factor family, plays a vital role in the regulation of osteogenesis. Recently, accumulating evidence demonstrated that RUNX2 is expressed at higher level in numerous human cancer tissues compared to their corresponding normal ones, indicating that RUNX2 might have a pro-oncogenic role. In this study, we have asked whether RUNX2 silencing could enhance gemcitabine (GEM) sensitivity of pancreatic cancer cells.
siRNA-mediated knockdown of RUNX2 increased GEM sensitivity of p53-null AsPC-1, p53-mutated MiaPaCa-2 and p53-mutated Panc-1 cells. Intriguingly, RUNX2 depletion caused a marked induction and activation of TAp73 and TAp63 in AsPC-1 cells and MiaPaCa-2/Panc-1 cells, respectively. Similar results were also obtained in spheres generated from MiaPaCa-2 cells. Thus, our present observations suggest that RUNX2 depletion improves GEM sensitivity of pancreatic cancer cells through the potentiation of TAp73/TAp63-dependent cell death pathway.

Free Research Field

生化学