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

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.

Suppression of hepatocellular carcinoma progression by long noncoding RNA apolipoprotein C1 pseudogene via the regulation of the microRNA-106b-PTEN axis

“…Within the mechanism of lncRNA acting as a ceRNA of miRNA in further regulating the target protein of miRNA, PTEN acts as the target of miR-106b, as indicated by Shi et al ’s findings ( 23 ) and those of our luciferase reporter assays. PTEN was first discovered to be a tumor suppressor in 1997 and has been studied in depth since then ( 24 , 25 ). In esophageal squamous cell carcinoma, miR-106b contributes to invasion and metastasis by regulating PTEN-mediated epithelial-to-mesenchymal transition ( 16 ).…”

Extracellular Vesicles in Breast Cancer: From Intercellular Communication to Therapeutic Opportunities

“…The upregulation of PI3K/AKT signalling in breast cancer tissues decreases the sensitivity of these cells to apoptosis induction. However, the tumour suppressor gene phosphatase and tensin homolog (PTEN) acts as a negative regulator of the PI3K pathway by antagonizing its signalling [75]. PTEN dephosphorylates a lipid product required for AKT activation, thus inhibiting the PI3K pathway.…”

Carbon Nanotube-Mediated Delivery of PTEN Variants: In Vitro Antitumor Activity in Breast Cancer Cells

“…The tumor-suppressing function of PTEN relies on its ability to decrease the augmented concentrations of phosphatidylinositol-3,4,5-triphosphate (PIP3), which are produced by the phosphoinositide-3 lipid kinases (PI3’Ks) [ 5 , 6 , 7 , 8 ]. PIP3 serves as a critical lipid secondary messenger in the process of tumorigenesis, activating signaling molecules involved in various cellular processes, including survival, proliferation, cell motility, and invasion [ 8 , 9 , 10 ]. Mutations in the PTEN gene or its promoter are widespread, at a rate close to p53.…”