Involvement of MyoD and PEA3 in regulation of transcription activity of MDR1 gene.
Overexpression of multidrug resistance 1 (MDR1) in cancer remains one of the major causes for the failure of chemotherapy. In the present study, we found that MyoD and PEA3 could activate P-glycoprotein (P-gp) expression in SGC7901 cells. Knockdown of MyoD and PEA3 attenuated MDR1 expression and increased the sensitivity of multidrug resistant cancer cells to cytotoxic drugs that were transported by P-gp in SGC7901/VCR cells. MyoD or PEA3 could bind to the E-box and PEA3 sites on the MDR1 promoter and activate its transcription. The regulation of MDR1 expression by MyoD and PEA3 may provide potential ways to overcome MDR in cancer treatment.
Zhao
Yaxin
Y
Department of general surgery, The Second Affiliated Hospital of Wenzhou Medical College, China.
Liu
Jiefan
J
Hong
Qi
Q
Yang
Chen
C
Chen
Li
L
Chen
Ying
Y
Wang
Qiaoqiao
Q
Zhao
Kuaile
K
Jin
Wei
W
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019450:Genes, MDR; D006801:Humans; D017570:MyoD Protein / Q000494:pharmacology*; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology; D014157:Transcription Factors / Q000494:pharmacology*; D015533:Transcriptional Activation / Q000187:drug effects*
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017570:MyoD Protein; D014157:Transcription Factors; C065788:transcription factor PEA3