The role of c-myc in regulating mdr1 gene expression in tumor cell line KB.
OBJECTIVE
To investigate the relationship between c-myc expression and mdr1 regulation in multidrug resistance (MDR) tumor cell line KBv200.


METHODS
A DNA sequence encoding the ribozyme gene was incorporated into a eukaryotic expression vector (pH beta Apr-1 neo) and transfected into the cell line KB, which is resistant to vincristine and expresses the MDR phenotype. The changes of c-myc protein, P-glycoprotein (P-gp) and c-myc mRNA in the KB cell line were assessed before and after treatment with anti-mdr1-ribozyme using immunohisto-chemistry, flow cytometry and semi-quantitative RT-PCR methods.


RESULTS
The results demonstrate elevated levels of c-myc mRNA and c-myc protein as well as P-gp in KBv200 cells which are resistant to vincristine (VCR), compared to these of the KB cell which is not resistant to VCR. The expression of c-myc protein, P-gp and c-myc mRNA in the multidrug resistant cell, KBv200, displayed higher than that in the sensitive cell, KB. However, after reversing the multidrug resistance phenotype by anti-mdr1-ribozyme, the level of c-myc protein, P-gp and c-myc mRNA expression showed significant down-regulation in KBv/5 mR3, without difference in KB/5 mR3 and KB.


CONCLUSIONS
The results of our study suggest that there is a close relationship between c-myc gene and mdr1 gene. c-myc may be involved in regulating the expression of mdr1.
He
Y
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Department of Otorhinolaryngology, Nanfang Hospital, First Military Medical University, Guangzhou 510510, China.
Zhang
J
J
Zhang
J
J
Yuan
Y
Y
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D010641:Phenotype; D010957:Plasmids / Q000235:genetics; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014750:Vincristine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D016337:RNA, Catalytic; D012333:RNA, Messenger; D014750:Vincristine