<Originals>Mechanisms of retinoid resistance in a myeloid cell line, YM711,transfected with PML/RARα cDNA : possible involvement of redox potential

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概要

• 論文の詳細を見る

• We established a myeloid cell line (YM711) by transfecting exogenous PML/RARα cDNA into peripheral blood stem cells. The established cells were positive for CD33,CD34,CD38,CD13,CD14,and CD11b. Cytochemical examination also revealed YM711 cells to be positive for peroxidase, α-naphtyl butyrate esterase, and acid phosphatase. Although PML/ RARα mRNA was detected by reverse-transcription and polymerase chain reaction (RT-PCR) in YM711 cells, all-trans retinoic acid (ATRA) did not induce differentiation of these cells. We, therefore, designated the YM711 as being ATRA resistant. Because YM711 expressed multi-drug resistance 1 (MDR-1) mRNA and cell surface p-glycoprotein, we assessed whether verapamil and ATRA would induce the differentiation of YM711 and found not. Increased expression of cellular retinoic acid-binding protein-II (CRABP-II) was also detected on YM711 cells. We tried to suppress the expression of CRABP-II mRNA in vitro by using antisense-Soligonucleotides for CRABP-II mRNA. However differentiation of YM711 was not observed in the presence of 10^<-5> M ATRA. To induce differentiation of this cell line, we then focused on redox regulation. We used thiol compounds-free RPMI 1640 medium, and mixed this with regular RPMI 1640 at the ratio of 3 : 7. After 4 days in culture with the 3 : 7 medium, the expression of CD14 on YM711 cells was enhanced significantly following the treatment with 10^<-6> M ATRA. In conclusion, we suggest that redox status is an important factor for ATRA-induced differentiation of the ATRA-resistant cell line. Furthermore, this cell line may be useful in elucidating the mechanism of resistance of leukemia cells to retinoids.

• 近畿大学の論文

著者

• Maeda Yasuhiro

  Third Department Of Internal Medicine Kinki University School Of Medicine

• Maeda Yasuhiro

  近畿大学 第3内科

• YAMAMURA Masaomi

  Nagasaki CML Study Group

• ANDO Kiyoshi

  Tokai University

• Kanamaru A

  Department Of Hematology Kinki University School Of Medicine

• Maeda Yasuhiro

  Department Of Hematology Nephrology And Clinical Immunology Kinki University School Of Medicine

• Matsuda M

  Third Department Of Internal Medicine Kinki University School Of Medicine

• KANAMARU Akihisa

  Third Department of Internal Medicine, Kinki University School of Medicine

• SUMIMOTO Yoshiyasu

  Third Department of Internal Medicine, Kinki University School of Medicine

• Nawata Hiroyuki

  Third Department Of Internal Medicine Kinki University School Of Medicine

• MATSUDA Mitsuhiro

  Third Department of Internal Medicine, Kinki University School of Medicine

• Kanamaru Akihisa

  Division Of Hematology Nephrology And Rheumatology Department Of Internal Medicine Kinki University

• Kanamaru Akihisa

  Third Department Of Internal Medicine Kinki University School Of Medicine

• Morita Yasuyoshi

  Third Department Of Internal Medicine Kinki University School Of Medicine

• Maeda Yasuhiro

  Drug Safety Research Laboratory Taiho Pharmaceutical Co. Ltd.

• Kikuchi Ako

  Department Of Hematology/oncology Tokai University School Of Medicine

• Kikuchi Ako

  Tokai University

• Miyazaki Yasushi

  Department Of Hematology Tama Hokubu Medical Center

• Kanamaru Akihisa

  Division Of Hematology And Oncology Department Of Medicine Tokai University School Of Medicine

• 松田 光弘

  熊本大 大学院自然科学研究科

• Maeda Yasuhiro

  Department Of Applied Physics Tokyo Institute Of Technology

• Ando Kiyoshi

  Department Of Hematology And Oncology Tokai University

• Sumimoto Yoshiyasu

  Third Department Of Internal Medicine Kinki University School Of Medicine

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