The effects of the tumor suppressor gene PTEN on the proliferation and apoptosis of breast cancer cells via AKT phosphorylation

Junhua Zhang; Ying Zhang; Xiaomeng Lin; Xiaoxu Han; Kenneth L Meredith; Zhong Li

doi:10.21037/tcr-23-826

The effects of the tumor suppressor gene PTEN on the proliferation and apoptosis of breast cancer cells via AKT phosphorylation

Transl Cancer Res. 2023 Jul 31;12(7):1863-1872. doi: 10.21037/tcr-23-826. Epub 2023 Jul 28.

Authors

Junhua Zhang^#¹, Ying Zhang^#¹, Xiaomeng Lin¹, Xiaoxu Han¹, Kenneth L Meredith², Zhong Li¹

Affiliations

¹ Department of Breast Surgery, Affiliated Hospital of Hebei University, Baoding, China.
² Florida State University College of Medicine, Tallahassee, FL, USA.

^# Contributed equally.

Abstract

Background: The proliferation and apoptosis of cancer cells play important roles in breast carcinomas. However, to date, there have been few reports on the correlation between the expression of PTEN and AKT phosphorylation in breast cancer. This present study investigated the effects of the phosphatase and tensin homology deleted from chromosome 10 (PTEN) gene on the proliferation and apoptosis of breast cancer cells through protein kinase B (AKT) phosphorylation.

Methods: Human breast cancer MDA-MB-231 cells were transfected with the pcDNA3.0 control vector or the pcDNA3.0-PTEN vector for 48 hours. The Cell Counting Kit 8 (CCK-8) was used to detect cell survival rates, double staining was performed to detect apoptosis, and Western blot (WB) analysis was conducted to detect protein expression. The effects of PTEN expression on the cell cycle and apoptosis of human breast cancer cell line MDA-MB-231, and on the levels of phosphorylated AKT protein were further analyzed. Moreover, the relationship between the PTEN gene and clinical features were also analyzed.

Results: The cell survival rate of cells transfected with pcDNA3.0-PTEN was significantly lower than that of cells transfected with the control pcDNA3.0 vector (55.65%±12.18% vs. 97.32%±12.45%, P=0.004). Compared with the pcDNA3.0 group, the apoptosis rate of the pcDNA3.0-PTEN group was significantly increased (20.65±2.18 vs. 2.32±0.45, P=0.001). The expression of PTEN protein in pcDNA3.0-PTEN group was higher than that in the pcDNA3.0 group, and the expression of the AKT and mTOR proteins was significantly lower than that in pcDNA3.0 group (P<0.05). The expression of PTEN in the lymph node metastasis positive group was significantly higher than that in the lymph node metastasis negative group (P<0.05). The expression of the AKT protein in breast cancer was higher than that in normal breast tissue, and the difference was statistically significant (P<0.01).

Conclusions: Overexpression of the PTEN gene can promote AKT phosphorylation, increase the apoptotic index of breast cancer cells, and reduce the proliferative activity of breast cancer cells. This provided a new direction for the next treatment of breast cancer, but further clinical research is needed.

Keywords: PTEN gene; breast cancer; cell proliferation; mechanism research; phosphorylation.