Tax of the human T-lymphotropic virus type I transactivates promoter of the MDR-1 gene.
The mdr-1 gene has been shown to confer resistance to chemotherapy of multiple drugs which share no obvious structural similarities. We and others have previously reported that some virus-associated malignant cells express high levels of MDR-1 (1,2), probably regulated by some viral proteins. In this study we have examined the role of Tax, the key protein of HTLV-1. An excellent correlation was found between the existence of HTLV-1 and the expression of MDR-1 among seven human T-cell lines. In the second part of the study, a 1. 76-kb DNA fragment representing the upstream regulatory elements of human mdr-1 gene was cloned into the CAT reporter plasmid. When the Tax expression plasmid was co-transfected with the MDR-1 reporter plasmid, a significant induction of CAT activity was observed. We conclude that Tax protein may up-regulate the expression of the mdr-1 gene.
Chuang
S E
SE
Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan, Republic of China.
Doong
S L
SL
Lin
M T
MT
Cheng
A L
AL
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D016356:Gene Products, tax / Q000235:genetics* / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D015533:Transcriptional Activation
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D016356:Gene Products, tax