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Relationship Between HSP70 and ERBB2 Expression in Breast Cancer Cell Lines Regarding Drug Resistance
L U Yue1, Jin-Yu Xiang2, Ping Sun2
1Department of Oncology, Qingdao Municipal Hospital, School of Medicine, Qingdao University, Qingdao, P.R. China.
Background:
Heat shock protein 70 (HSP70) is known to be downstream of human epidermal growth factor receptor-2 (ERBB2), but little is known regarding the relationship between HSP70 and drug resistance mediated by ERBB2 in breast cancer.
Materials And Methods:
After infecting breast cancer cells with lentivirus-mediated Lenti-ShHSP70 and Lenti-ShERBB2, we examined the expression of HSP70 and ERBB2 by real-time polymerase chain reaction and western blotting.
Results:
Compared to the control groups, mRNA expression of HSP70 was decreased in lentivirus-infected, and western blotting indicated a concordant reduction of HSP70 protein. On the other hand, ERBB2 was significantly down-regulated by HSP70 silencing in SK-BR-3 cells at both the mRNA and protein levels. Expression of HSP70 in transfected cells was also reduced by Lenti-ShERBB2. CCK8 viability assay indicated that inhibition of HSP70 increased the sensitivity of SK-BR-3 cells to fluorouracil treatment.
Conclusion:
HSP70 affects ERBB2 and ERBB2-mediated drug-resistance in breast cancer cells.
Insights
Heat shock protein 70 (HSP70) affects human epidermal growth factor receptor-2 (ERBB2) expression and ERBB2-mediated drug resistance in breast cancer. Silencing HSP70 enhances sensitivity to fluorouracil treatment in SK-BR-3 cells.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Heat shock protein 70 (HSP70) is a downstream target of human epidermal growth factor receptor-2 (ERBB2).
- The precise role of HSP70 in ERBB2-mediated drug resistance in breast cancer remains largely unexplored.
Purpose of the Study:
- To investigate the relationship between HSP70 and ERBB2.
- To determine the impact of HSP70 on ERBB2-mediated drug resistance in breast cancer cells.
Main Methods:
- Breast cancer cells (SK-BR-3) were infected with lentivirus vectors to silence HSP70 (Lenti-ShHSP70) and ERBB2 (Lenti-ShERBB2).
- Gene and protein expression levels of HSP70 and ERBB2 were analyzed using real-time polymerase chain reaction and western blotting.
- Cell viability was assessed using the CCK8 assay to evaluate drug sensitivity.
Main Results:
- Silencing HSP70 led to a significant down-regulation of both ERBB2 mRNA and protein levels in SK-BR-3 cells.
- ERBB2 silencing also reduced HSP70 expression.
- Inhibition of HSP70 increased the sensitivity of SK-BR-3 cells to fluorouracil treatment, as indicated by the CCK8 assay.
Conclusions:
- HSP70 plays a crucial role in regulating ERBB2 expression.
- HSP70 is implicated in ERBB2-mediated drug resistance in breast cancer.
- Targeting HSP70 may represent a therapeutic strategy to overcome drug resistance in ERBB2-positive breast cancer.
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