Molecular mechanisms behind the acquisition of multi-drug resistance in sphere-formed colon cancer cells.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590496
• 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: SHIMOZATO Osamu 千葉県がんセンター(研究所), 研究所・発がん研究グループ, 上席研究員 (30344063)
• Co-Investigator(Kenkyū-buntansha): KAMIJO Takehiko 埼玉県立がんセンター(臨床腫瘍研究所), 臨床腫瘍研究所, 所長 (90262708) ; SOUDA Hiroaki 千葉県がんセンター(研究所), 医療局・消化器外科, 主任医長 (90261940)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 大腸がん / 癌性幹細胞 / スフェア形成 / 治療抵抗性 / CD133

Outline of Final Research Achievements

Multi-drug resistance (MDR) has been considered to be one of the major courses of cancer recurrence after treatment. Recent studies demonstrated that a small population of cancer cells, termed cancer stem cells (CSCs), is involved in tumorigenesis and MDR. We therefore sought to examine the molecular mechanism(s) behind the acquisition of drug resistant property of colon cancer-derived sphere cells where CSCs accumulate. Under our experimental conditions, sphere-formed cells clearly exhibited MDR mediated by a drug efflux protein ABCB1. Intriguingly, ABCB1 expression was epigenetically repressed by a histone demethylase, JHDM1B, which was down-regulated in sphere-formed cells. Furthermore, a lower expression level of JHDM1B as well as a higher expression level of ABCB1 was closely associated with poor prognosis of colon cancer patients treated with adjuvant chemotherapy. Together, our observations strongly suggest that JHDM1B plays a central role in the regulation of MDR in colon CSCs.

Free Research Field

分子生物学・細胞生物学・腫瘍生物学