RCAN1,, HL60, calcineurin, NFAT
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- Erika Walters
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1 RCAN1 calcineurin RCAN1 1) 2) calcineurin-nfat RCAN1 RCAN1 RCAN1 is involved in the regulation of cell functions including inhibition of calcineurin. In this study, we found that RCAN1 is extraordinarily expressed in leukemia cells. Furthermore, we revealed that RCAN1 is important for cell growth, particularly under undesirable conditions of low serum concentration. In leukemia cells, calcineurin-nfat signaling has been shown to be one of the targets of RCAN1. We also identified several molecules, which could directly bind with RCAN RCAN1,, HL60, calcineurin, NFAT 1. (AML) AML RCAN1 Ca 2+ /Calmodulin calcineurin NF-AT NF-kB Down RCAN1 calcinuirin
2 RCAN1 Down RCAN1 RCAN1 RCAN1 RCAN1 2. RCAN1 3. (1) RCAN1 1(AML) (THP-1HL60U937) (Jurkat, Raji) (CML)(KCL22K562 KU812) (RPMI8226U266) RNA Superscript II reverse transcriptase cdna Reverse transcriptase-polymerase chain reaction(rt-pcr) RCAN1 mrna RCAN1 Western Blot RCAN1 2AML CML RNA RCAN1 mrna RT-PCR real-time PCR real-time PCR ABI PRISM 7700 system (2) RCAN1 FACSaria (Becton Dickinson) FACS CD34 CD38CD14CD16CD33 RCAN1 mrna RT-PCR real-time PCR (3) AML RCAN1 pll3.7 3 RCAN1 shrna RCAN1 shrna HL60 RCAN1 shrna RCAN1 Western Blot RCAN1 (4) RCAN1 Calcineurin-NFAT signaling RCAN1 shrna HL60 RCAN1 calcineurin NFAT4 Western Blot RCAN1 calcineurin cyclosporine A (5) RCAN1 RPMI8226 U266 RCAN1 shrna (6) Two-hybrid screening RCAN1 RCAN1 cdna Bait K562 Prey Yeast two-hybrid screening 4. (1) RCAN1 RCAN1 mrna RT-PCR RCAN1 RCAN1-1 Western Blot
3 (2) AML CML RCAN1 6 AML RCAN1 mrna 1%RCAN1 a) b) RCAN1 c)cleaved caspases cleaved PARP CML RCAN1 (3) RCAN1 FACS CD34+CD38- CD34+CD38+ CD33+CD14-CD16- CD33+CD14+ CD33+CD16+ RCAN1 RT-PCR real-time PCR RCAN1 CML RCAN1 (5) Calcineurin-NFAT signaling RCAN1 HL60 RCAN1 shrna a)calcineurin b) NFAT4 c) NFAT4 (4) RCAN1 RCAN1 shrna HL60 IL-3 32D RCAN1 L-3
4 HL60 RCAN1 calcineurin NFAT4 calcineurin cyclosporine A RCAN1 RCAN1 calcineurin RCAN1 (6) RCAN1 RPMI8226 U266 RT-PCR RCAN1-1 CD138 RCAN RCAN1 RCAN1 (8) RCAN1-2768bp RCAN1 pgl4.17[luc2/neo] deletion mutants KCL bp -866 bp RCAN1 (7) RCAN1 RPMI8226 RCAN1 shrna U266 PLL3.7 RPMI8226 U bp-866 bp -459bp -249bp TGIFHNF-4 USF RCAN1 (9) RACN1 RCAN1 cdna Bait K562 Prey Yeast two-hybrid screening
5 HINT1, HINT2 LINT1 RCAN1 in vitro translation pmx RCAN (1) Nagai, T., Ohmine, K., Fujiwara, S., Uesawa, M., Sakurai, C., and Ozawa, K.: Combination of tipifarnib and rapamycin synergistically inhibits the growth of leukemia cells and overcomes resistance to tipifarnib via alteration of cellular signaling pathways. Leukemia Res. 34: , DOI: /j.leukres. (2) Nagai, T., Takeuchi, J., Usui, N : Imatinib for Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia: Results of a Prospective Study in Japan. Int J Hematol. 92: , DOI: /s x. (3) Tatara, R., Nagai, T., Kobayashi, H., Hatano, K., Suzuki, T., Muroi, K., and Ozawa, K. AA amyloidosis associated with macroglobulinemia. (Letter) Int J Hematol. 92: , DOI: /s z. (4) Sato, K., Ozaki, K., Matsuyama, T., Ohmine, K., Suzuki, T., Mori, M., Nagai, T., Muroi, K., and Ozawa, K.: Incidental carcinomas detected by PET/CT scans in patients with malignant lymphoma. Int J Hematol. 92: , DOI: /s x. (5) Yoshida, K., Nagai, T., Ohmine, K., Uesawa, M., Sripayap, P., Ishida, Y., and Ozawa, K.: Vincristine potentiates the anti-proliferative effect of an aurora kinase inhibitor, VE-465, in myeloid leukemia cells. Biochem. Pharmcol. 82: , DOI: /j.bcp. (6) Kikuchi, Y., Kume, A., Urabe, M., Mizukami, H., Suzuki, T., Ozaki, K., Nagai, T., and Ozawa, K.: Reciprocal upregulation of Notch signaling molecules in hematopoietic progenitor and mesenchymal stromal cells. J Stem Cells Regenerative Med. 7: 61-68, htm (7) Meguro, A., Nagai, T., Ozawa, K : Rituximab plus 70% cyclophosphamide, doxorubicin, vincristine and prednisone for Japanese patients with diffuse large B-cell lymphoma aged 70 years and older. Leuk Lymphoma. 53: 43-49, DOI: / (8) Oka, S., Nagai, T., Hanafusa, T. 910 : Prediction of progression from refractory cytopenia with unilineage dysplasia by analysis of bone marrow blast cell composition. J Clin. Exp. Hematop. 52: 63-66, DOI: (9) Sato, K., Nagai, T., Izumi, T., Ohmine, K., Ozaki, K., Muroi, K., and Ozawa, K.: Rituximab-induced interstitial pneumonia due to CD8-positive T-cell infiltration. Acta Haematologica. 128: , DOI: / (10) Kobayashi, H., Nagai, T., Muroi, K. 8 9 : Autologous hematopoietic recovery with aberrant antigen expression after allogeneic bone marrow transplantation. J Clin. Exp. Hematop. 52: 81-83, DOI: (11) Nagai, T., Suzuki, T., Komatsu, N., Hosokawa, K., Nakao, S., and Ozawa, K.: Alteration of chromosome 13 abnormalities after therapeutic heamatopoiesis recovery in myelodysplastic syndrome. Open J Hematol.
6 3-7, DOI: /ojhmt_3_1_ (1) Fujiwara, S.: Extraordinary expression of RCAN1 Crucial to leukemia progression (2) Fujiwara, S.: Crucial role of RCAN1 in leukemia progression (3) Uesawa, M.: Cloning of 5-azacitidine-resistant acute myeloid leukemia cell lines, THP-1/AR and HL60/AR. The 2 nd JSH International Symposium, Nagasaki, 2011 (4) Sripayap, P.: Cloning and characterization of 5-azacitidine-resistant human AML cell lines, THP-1/AR and HL60/A (5) Sripayap, P.: Histone deacetylase inhibitor romidepsin overcomes AZA-resistance in AZA-resistant cell lines. The 3 rd JSH International Symposium, Kawagoe, Japan, 2012 (6) Sripayap, P.: Overcoming resistance to 5-azacytidine in acute myeloid leukemia. The 54th Annual Meeting of American Society for Hematology, Atlanta, USA, 2012 (7) Kobayashi, H.: Analysis of primary small intestinal lymphoma diagnosed with double-balloon endoscopy (8) Sripayap, P.: Histone deacetylase inhibitor romidepsin overcomes 5-azacytidine (AZA) resistance (FUJIWARA SHIN-ICHIRO) (1) NAGAI TADASHI (2) (3) OHMINE KEN
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