Dataset Information

Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.

ABSTRACT: Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PTEN tumor suppressor on TNBC clinical behavior, prognosis, and multidrug resistance (MDR), using immunohistochemistry and copy number analysis by quantitative real-time PCR. Our results revealed that loss of PTEN and high expression of PI3K and mTOR proteins are associated with poor outcome of TNBC patients. PTEN deletions appeared as a major cause of reduced or absent PTEN expression in TNBC. Importantly, homozygous deletions of PTEN (and not hemizygous deletions) are a potential molecular marker of metastasis formation and good predictors of TNBC outcome. In conclusion, we believe that concurrent examination of PTEN/PI3K/mTOR protein expression may be more useful in predicting TNBC clinical course than the analysis of single protein expression. Specifically, our results showed that PTEN-reduced/PI3K-high/mTOR-high expression constitutes a 'high risk' profile of TNBC.

SUBMITTER: Prvanovic M

PROVIDER: S-EPMC8621563 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.

Prvanović Mirjana M Nedeljković Milica M Tanić Nasta N Tomić Tijana T Terzić Tanja T Milovanović Zorka Z Maksimović Zlatko Z Tanić Nikola N

Life (Basel, Switzerland) 20211117 11

Breast cancer is the most commonly occurring malignancy and the leading cause of cancer-related death in women. Triple-negative breast cancer (TNBC) is the most aggressive subtype and is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival. The aim of this study was to investigate the PI3K/PTEN/Akt/mTOR pathway as one of the most frequently deregulated pathways in cancer. We aimed to explore the impact of PI3K and mTOR oncogenes as well as the PT ...[more]

PMID: 34833123

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Project description:Pseudolaric acid B (PAB), a diterpene acid isolated from the root bark of Pseudolarix kaempferi, has been shown to exert strong antitumor properties. The aim of the present study was to investigate the mechanisms underlying the proposed antitumor properties of PAB in the triple‑negative breast cancer cells, MDA‑MB‑231. The cell processes evaluated included cell proliferation by Cell Counting Kit‑8 assay, colony formation and EdU assay, apoptosis by Annexin V‑FITC/PI apoptosis assay, cell migration by Transwell migration assay and invasion by Transwell invasion assay. PAB significantly inhibited the proliferation of MDA‑MB‑231 cells through a mechanism that was considered to be associated with cell cycle arrest at the G2/M phase. There was decreased protein expression levels of CDK1 and cyclin B1 and increased protein expression levels of p53 and p21. However, there were no well‑defined inhibitory effects on the normal breast cell line MCF10A. PAB also triggered apoptosis in a concentration‑dependent manner through the mitochondrial apoptosis pathway. It caused collapse of mitochondrial membrane potential, accumulation of reactive oxygen species and release of cytochrome c, as well as upregulation of cleaved caspase‑3, cleaved caspase‑9, cleaved PARP and Bax, and downregulation of Bcl‑2 and Bcl‑xl. The migration and invasion ability of MDA‑MB‑231 cells were inhibited by decreasing the expression levels of the epithelial‑mesenchymal transition‑related markers N‑cadherin and vimentin and increasing the expression of E‑cadherin. Moreover, the expression levels of PI3K (p110β), phosphorylated (p)‑AKT (ser473) and p‑mTOR (ser2448) were downregulated and LY294002, a PI3K inhibitor, could interact additively with PAB to induce apoptosis of MDA‑MB‑231 cells. Overall, the present results demonstrated that PAB induced apoptosis via mitochondrial apoptosis and the PI3K/AKT/mTOR pathway in triple‑negative breast cancer. It also inhibited cellular proliferation, migration and invasion, suggesting that PAB may be a useful phytomedicine for the treatment of triple‑negative breast cancer.

Dataset Information

Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.

Publications

Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer.

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