J Breast Cancer.  2019 Jun;22(2):172-184. 10.4048/jbc.2019.22.e21.

Overexpression of Tumor Protein p53-regulated Apoptosis-inducing Protein 1 Regulates Proliferation and Apoptosis of Breast Cancer Cells through the PI3K/Akt Pathway

Affiliations
  • 1Department of Breast Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2Department of Breast & Thyroid Surgery, Southwest Hospital, Third Military Medical University(Army Medical University), Chongqing, China.
  • 3Department of Breast & Thyroid Surgery, The First People's Hospital of Yunnan Province, Kunming, China. jialiu_lj12@163.com

Abstract

PURPOSE
Tumor protein p53-regulated apoptosis-inducing protein 1 (TP53AIP1) functions in various cancers. We studied the effect and molecular mechanism of TP53AIP1 in breast cancer.
METHODS
The degree of correlation between TP53AIP1 expression and overall survival in patients with breast cancer was obtained from the online The Cancer Genome Atlas database. Six of the TP53AIP1 levels in the tumor and adjacent non-tumor tissues randomly selected from 38 breast cancer patients were determined. Transgenic technology was used to enhance the expression of TP53AIP1 in breast cancer cell lines, MDA-MB-415 and MDA-MB-468, and to observe the effects of gene overexpression on the proliferation, cell cycle, and apoptosis of breast cancer cells. The molecular mechanism of association between cell cycle- and apoptosis-related factors and the phosphoinositide 3-kinases/protein kinase B (PI3K/Akt) pathway was also studied.
RESULTS
The messenger RNA and protein expression levels of TP53AIP1 in cancer tissues were significantly lower than those in the control group. TP53AIP1 overexpression inhibits cell viability. The mechanism of TP53AIP1 inhibition of proliferation and growth of breast cancer cells includes cell cycle arrest, apoptosis promotion (p < 0.01), promotion of the expression of cleaved-caspase-3 (p < 0.01), cleaved-caspase-9 (p < 0.01), B cell lymphoma/leukemia-2 (Bcl-2)-associated X protein, and p53 (p < 0.01), and the inhibition of Bcl-2, Ki67, and PI3K/Akt pathways (p < 0.01).
CONCLUSION
TP53AIP1 may be a novel tumor suppressor gene in breast cancer and can potentially be used as an effective target gene for the treatment of breast cancer.

Keyword

Apoptosis; Breast neoplasms; Cell proliferation; Genes, p53

MeSH Terms

Apoptosis*
Breast Neoplasms*
Breast*
Cell Cycle Checkpoints
Cell Line
Cell Proliferation
Cell Survival
Genes, p53
Genes, Tumor Suppressor
Genome
Humans
Phosphotransferases
RNA, Messenger
Phosphotransferases
RNA, Messenger
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