Multidrug resistance in breast cancer cells during epithelial-mesenchymal transition is modulated by breast cancer resistant protein.
OBJECTIVE
Epithelial-mesenchymal transition (EMT) not only initiates invasion and metastasis of tumors, but also induces multidrug resistance in tumor cells. Our experiment analyzed the dependability between breast cancer resistant protein (BCRP) and EMT in breast cancer to explore the effect of EMT on BCRP-mediated multidrug resistance.


METHODS
The expressions of BCRP and transcription inhibitor Snai1 (Snail) in breast cancer were detected by immunohistochemistry. The eukaryotic expression vector pCDNA3.1-Snail was constructed and then transfected into human breast cancer cell line MCF-7. Snail, epithelial marker gene E-cadherin, interstitial marker gene Vimentin, multidrug resistance protein BCRP, and relative drug resistance were measured by immunofluorescence, Western blot, real-time polymerase chain reaction (PCR), and MTT assay.


RESULTS
Immunohistochemistry showed that Snail was highly correlated with BCRP in breast cancer. Immunofluorescence, Western blot, real-time PCR revealed that compared with parent cell MCF-7, after transfected with Snail, the expression of E-cadherin in MCF-7 decreased, but Snail, Vimentin, and BCRP increased. MTT displayed that the relative drug resistance increased to 9.93.


CONCLUSIONS
After transfected with eukaryotic expression vector pCDNA3.1-Snail, breast cancer cells MCF-7 showed EMT with BCRP-mediated multidrug resistance.
Chen
Wei-Juan
WJ
Department of Pathology, Weifang Medical University, Weifang, Shandong 261041, PR China.
Wang
Hui
H
Tang
Yong
Y
Liu
Chuan-Liang
CL
Li
Hong-Li
HL
Li
Wen-Tong
WT
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D008875:Middle Aged; D008942:Mitoxantrone / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D012333:RNA, Messenger / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D015820:Cadherins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; D008942:Mitoxantrone