Overexpression of CDHR2 inhibits proliferation of breast cancer cells by inhibiting the PI3K/Akt pathway
10.12122/j.issn.1673-4254.2024.06.12
- VernacularTitle:CDHR2过表达通过抑制PI3K/Akt通路抑制乳腺癌细胞增殖
- Author:
Jincun FANG
1
,
2
,
3
;
Liwei LIU
;
Junhao LIN
;
Fengsheng CHEN
Author Information
1. 南方医科大学中西医结合医院肝病科,广东 广州 510315
2. 南方医科大学附属何贤纪念医院肿瘤科,广东 广州 511400
3. 南方医科大学第三临床医学院,广东 广州 510630
- Keywords:
breast cancer;
CDHR2;
PI3K/Akt pathway;
proliferation;
cell cycle
- From:
Journal of Southern Medical University
2024;44(6):1117-1125
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which CDHR2 overexpression inhibits breast cancer cell growth and cell cycle pragression via the PI3K/Akt signaling pathway.Methods Bioinformatic analysis was performed to investigate CDHR2 expression in breast cancer and its correlation with survival outcomes of the patients.Immunohistochemistry was used to examine CDHR2 expressions in surgical specimens of tumor and adjacent tissues from 10 patients with breast cancer.CDHR2 expression levels were also detected in 5 breast cancer cell lines and a normal human mammary epithelial cell line using qRT-PCR and Western blotting.Breast cancer cell lines MDA-MB-231 and MCF7 with low CDHR2 expression were transfected with a CDHR2-overexpressing plasmid,and the changes in cell proliferation and cell cycle were evaluated using CCK-8 assay,EdU assay,and cell cycle assay;the changes in expressions of PI3K/Akt signaling pathway and cell cycle pathway proteins were detected with Western blotting.Results Bioinformatic analysis showed low CDHR2 expression level in both breast cancer and adjacent tissues without significant difference between them(P>0.05),but breast cancer patients with a high expression of CDHR2 had a more favorable prognosis.Immunohistochemistry,qRT-PCR and Western blotting showed that the expression of CDHR2 was significantly down-regulated in breast cancer tissues and breast cancer cells(P<0.01),and its overexpression strongly inhibited cell proliferation,caused cell cycle arrest,and significantly inhibited PI3K and Akt phosphorylation and the expression of cyclin D1.Conclusion Overexpression of CDHR2 inhibits proliferation and causes cell cycle arrest in breast cancer cells possibly by inhibiting the PI3K/Akt signaling pathway.