Role of MAPK/ERK signaling pathway in reversing endocrine resistance of breast cancer

doi:10.3969/j.issn.1673-8640.2022.04.008

Abstract

Abstract:

Objective To investigate the role of mitogen-activated protein kinase （MAPK）/extracellular regulated protein kinase （ERK） signaling pathway in reversing endocrine resistance of breast cancer. Methods Tamoxifen-resistant breast cancer cell lines,MCF-7/TAMR and T47D/TAMR,were established by human breast cancer cell lines,MCF-7 and T47D. The differences of cell proliferation and the expression of related MAPK/ERK signaling pathway molecules between MCF-7 and MCF-7/TAMR,T47D and T47D/TAMR were investigated. The suppressive effect of mitogen-activated protein kinase（MEK） inhibitor U0126 on MAPK/ERK signaling pathway in MCF-7/TAMR and T47D/TAMR was observed through the analysis of cell proliferation,cell cycle and transfactor expression. Results Compared with naïve MCF-7 or T47D cells,the proliferation and colony formation were increased （P<0.05,P<0.000 1）,and the expression of related MAPK/ERK signaling pathway molecules [phosphorylated extracellular regulated protein kinase（pERK）,ERK and c-MYC] was strongly increased. Suppressing MAPK/ERK signaling pathway by MEK inhibitor U0126,the growth of MCF7/TAMR or T47D/TAMR was decreased （P<0.000 1）,and cell cycle was arrested. The relative gene expression of transcription factors,steroid receptor coactivator-1（SRC-1）,E26 oncogene homolog-2（ETS-2） and c-JUN,and the expressions of their proteins were decreased by MEK inhibitor U0126（P<0.01）. Conclusions The inhibition of MAPK/ERK signaling pathway could reverse the endocrine resistance of breast cancer cells,which can provide a reference for the treatment of patients with endocrine resistant breast cancer.

Key words: Mitogen-activated protein kinase/extracellular regulated protein kinase signaling pathway, Transcription factor, Endocrine resistance, Breast cancer

CLC Number:

446.1

YE Jingwen, SHEN Yunyue, LIU Yiwen, HE Yiqing, DU Yan, ZHANG Guoliang, GAO Feng, YANG Cuixia. Role of MAPK/ERK signaling pathway in reversing endocrine resistance of breast cancer[J]. Laboratory Medicine, 2022, 37(4): 342-348.

Figures/Tables 7

References 24

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基因名称	序列（5'~3'）	产物长度/bp
SRC-1	F：ATCGGAGATCCTGCCAGCTTCA	75
	R：ATCGCCTGTTCCTGGTTGTCCA
ETS-2	F：GTGGGTGACATTCTCTGGGAACATC	142
	R：TGAGGAACGGAGGTGAGGTGTG
c-JUN	F：CCTTGAAAGCTCAGAACTCGGAG	172
	R：TGCTGCGTTAGCATGAGTTGGC
GAPDH	F：GTCTCCTCTGACTTCAACAGCG	95
	R：ACCACCCTGTTGCTGTAGCCAA

基因名称	序列（5'~3'）	产物长度/bp
SRC-1	F：ATCGGAGATCCTGCCAGCTTCA	75
	R：ATCGCCTGTTCCTGGTTGTCCA
ETS-2	F：GTGGGTGACATTCTCTGGGAACATC	142
	R：TGAGGAACGGAGGTGAGGTGTG
c-JUN	F：CCTTGAAAGCTCAGAACTCGGAG	172
	R：TGCTGCGTTAGCATGAGTTGGC
GAPDH	F：GTCTCCTCTGACTTCAACAGCG	95
	R：ACCACCCTGTTGCTGTAGCCAA

组别	S期		G2期
组别	MCF7/TAMR细胞	T47D/TAMR细胞	MCF7/TAMR细胞	T47D/TAMR细胞
对照组	18.81±0.12	10.80±0.17	14.22±0.10	17.89±0.17
U0126组
12 h	21.50±0.06	8.13±0.16	6.21±0.07	16.36±0.17
48 h	23.81±0.12	6.80±0.19	10.97±0.07	15.29±0.06

组别	S期		G2期
组别	MCF7/TAMR细胞	T47D/TAMR细胞	MCF7/TAMR细胞	T47D/TAMR细胞
对照组	18.81±0.12	10.80±0.17	14.22±0.10	17.89±0.17
U0126组
12 h	21.50±0.06	8.13±0.16	6.21±0.07	16.36±0.17
48 h	23.81±0.12	6.80±0.19	10.97±0.07	15.29±0.06