PMID- 11937269 OWN - NLM STAT- MEDLINE DCOM- 20021011 LR - 20211203 IS - 0301-472X (Print) IS - 0301-472X (Linking) VI - 30 IP - 4 DP - 2002 Apr TI - Human T-cell lymphotropic virus type I Tax activates lung resistance-related protein expression in leukemic clones established from an adult T-cell leukemia patient. PG - 340-5 AB - OBJECTIVE: We examined the significance of human T-cell lymphotropic virus type I (HTLV-I) Tax protein-induced resistance to anticancer drugs and the relationship between Tax and multidrug resistance proteins. MATERIALS AND METHODS: S1T cell, a leukemic non-Tax-producing T-cell clone established from an adult T-cell leukemia (ATL) patient, S1TcTax05 and S1TcTax10 clones, transfected with Tax stably expressing cDNA, and S1Tneo, transfected with a neomycin-resistant gene, were examined for Tax-related anticancer drug resistance. Resistance of those cells to the anticancer drugs doxorubicin, etoposide, cisplatin, and vindesine was tested with the MTT method. Expression of multidrug resistance protein mRNAs (MDR1, MRP1, cMOAT/MRP2, and LRP) was analyzed with reverse transcriptase polymerase chain reaction (RT-PCR). Doxorubicin subcellular distribution in those cells was examined by fluorescence microscopy. RESULTS: S1TcTax05 and S1TcTax10 showed resistance to doxorubicin, etoposide, and vindesine, but not to cisplatin as compared with S1T or S1Tneo. RT-PCR demonstrated that MRP1 mRNA was expressed, but MDR1, cMOAT, and LRP mRNAs were not in S1T or S1Tneo. Marked expression of LRP mRNA was detected, but no change of MDR1, MRP1, or cMOAT mRNA expression in Tax-expressing S1TcTax05 and S1TcTax10. Fluorescence microscopy demonstrated that doxorubicin was distributed mainly in the cytoplasm of S1TcTax05 and S1TcTax10, and in the nucleus of S1T and S1Tneo. CONCLUSIONS: These findings suggest that Tax-related drug resistance of ATL cells is due to LRP and not MDR1, as reported previously. These findings in cells derived from an ATL patient suggest a novel mechanism for drug resistance in Tax-expressing ATL cells. FAU - Sakaki, Yoshimune AU - Sakaki Y AD - First Department of Internal Medicine, Faculty of Medicine, Kagoshima University, Sakuragaoka 8-35-1, Kagoshima 890-8520, Japan. FAU - Terashi, Kenji AU - Terashi K FAU - Yamaguchi, Akihiko AU - Yamaguchi A FAU - Kawamata, Nakaaki AU - Kawamata N FAU - Tokito, Yuichi AU - Tokito Y FAU - Mori, Hiroyasu AU - Mori H FAU - Umehara, Megumi AU - Umehara M FAU - Yoshiyama, Takeshi AU - Yoshiyama T FAU - Ohtsubo, Hideo AU - Ohtsubo H FAU - Arimura, Kosei AU - Arimura K FAU - Arima, Naomichi AU - Arima N FAU - Tei, Chuwa AU - Tei C LA - eng PT - Journal Article PL - Netherlands TA - Exp Hematol JT - Experimental hematology JID - 0402313 RN - 0 (ABCC2 protein, human) RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 1) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Antineoplastic Agents) RN - 0 (Gene Products, tax) RN - 0 (Membrane Transport Proteins) RN - 0 (Multidrug Resistance-Associated Protein 2) RN - 0 (Multidrug Resistance-Associated Proteins) RN - 0 (RNA, Messenger) RN - 0 (Vault Ribonucleoprotein Particles) RN - 0 (major vault protein) RN - Y49M64GZ4Q (multidrug resistance-associated protein 1) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics MH - ATP-Binding Cassette Transporters/genetics/*metabolism MH - Adult MH - Antineoplastic Agents/pharmacokinetics MH - Cell Compartmentation MH - Clone Cells/metabolism/virology MH - Dose-Response Relationship, Drug MH - Gene Products, tax/*physiology MH - HTLV-I Infections/*pathology/virology MH - Human T-lymphotropic virus 1/chemistry MH - Humans MH - *Membrane Transport Proteins MH - Multidrug Resistance-Associated Protein 2 MH - Multidrug Resistance-Associated Proteins/genetics MH - RNA, Messenger/metabolism MH - Tumor Cells, Cultured MH - *Vault Ribonucleoprotein Particles EDAT- 2002/04/09 10:00 MHDA- 2002/10/12 04:00 CRDT- 2002/04/09 10:00 PHST- 2002/04/09 10:00 [pubmed] PHST- 2002/10/12 04:00 [medline] PHST- 2002/04/09 10:00 [entrez] AID - S0301472X02007750 [pii] AID - 10.1016/s0301-472x(02)00775-0 [doi] PST - ppublish SO - Exp Hematol. 2002 Apr;30(4):340-5. doi: 10.1016/s0301-472x(02)00775-0.