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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
[Relation between c-erbB1, c-erbB2, MAPK expression and resistance to tamoxifen in breast cancer cells in vitro]
Qing-yuan Zhang1, Wen-hui Zhao, Xin-mei Kang
1The Third Department of Internal Medicine, Tumor Hospital, Harbin Medical University, Harbin 150040, China. zhma19650210@163.com
Objective:
To study the growth regulation pathway and the mechanism of acquired resistance to tamoxifen (TAM) in breast cancer cells.
Methods:
TAM was used to induce wild-type MCF-7 human breast cancer cell line and establish a tamoxifen-resistant (TAM-R) cell line. RT-PCR, Western blot and immuocytochemical techniques were used to detect and compare mRNA and protein of c-erbB1, cerbB2, c-erbB3, c-erbB4 in wild-type MCF-7 and TAM-R MCF-7 cell lines.
Results:
Compared with wild-type MCF-7 cells, the mRNA of c-erbB1 increased 6 times (P < 0.05) and the protein 3 times higher (P < 0.05), and the mRNA of c-erbB2 increased 3 times (P < 0.05) and the protein 1.5 times higher (P < 0.05) in TAM-R MCF-7 cells. However, comparable levels of c-erbB3 mRNA and protein were expressed in both cell lines. c-erbB4 could not be detected. Under basic conditions, phosphorylated c-erbB1/c-erbB2 and c-erbB1/c-erbB3 heterodimers but not c-erbB2/c-erbB3 receptor heterodimers were detected in TAM-R cells in association with increased level of phosphorylated MAPK.
Conclusion:
Our findings demonstrated that the development of TAM-resistance in MCF-7 cells is related with the autocrine release and action of an c-erbB1-specific ligand inducing preferential c-erbB1/c-erbB2 dimerization and downstream activation of the MAPK pathway.
Insights
Tamoxifen resistance in breast cancer cells involves increased expression of c-erbB1 and c-erbB2 growth factor receptors. This resistance is linked to the MAPK pathway activation.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- Tamoxifen (TAM) is a widely used endocrine therapy for estrogen receptor-positive breast cancer.
- Acquired resistance to TAM remains a significant clinical challenge, necessitating a deeper understanding of its underlying mechanisms.
- Investigating growth factor receptor pathways offers potential targets for overcoming TAM resistance.
Purpose of the Study:
- To elucidate the growth regulation pathway in tamoxifen-resistant (TAM-R) breast cancer cells.
- To identify the molecular mechanisms driving acquired resistance to tamoxifen (TAM) in MCF-7 cells.
Main Methods:
- Established a TAM-resistant MCF-7 cell line from a wild-type counterpart.
- Utilized RT-PCR, Western blot, and immunocytochemistry to quantify c-erbB family receptor (c-erbB1-4) mRNA and protein levels.
- Assessed receptor dimerization and downstream signaling pathway activation (MAPK).
Main Results:
- TAM-resistant MCF-7 cells exhibited significantly increased mRNA and protein levels of c-erbB1 and c-erbB2 compared to wild-type cells.
- Comparable expression of c-erbB3 was observed; c-erbB4 was undetectable.
- Activated MAPK signaling was associated with c-erbB1/c-erbB2 and c-erbB1/c-erbB3 heterodimers in TAM-R cells.
Conclusions:
- Acquired TAM resistance in MCF-7 cells is associated with the autocrine release of c-erbB1 ligands.
- This leads to preferential c-erbB1/c-erbB2 dimerization and subsequent activation of the MAPK pathway.
- Targeting these receptor interactions may offer a strategy to overcome TAM resistance in breast cancer.
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