Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer
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Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia
2
Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia
3
Department of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences “Vinča”, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia
4
Department of Pathology, Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia
5
Public Health Institution Hospital “Sveti Vracevi”, 76300 Bijeljina, Republika Srpska, Bosnia and Herzegovina
6
Department of Neurobiology, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia
*
Author to whom correspondence should be addressed.
Academic Editors: Ui-Soon Khoo, Ho Tsoi and Man-Hong Leung
Life 2021, 11(11), 1247; https://doi.org/10.3390/life11111247
Received: 23 September 2021
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Revised: 5 November 2021
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Accepted: 11 November 2021
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Published: 17 November 2021
(This article belongs to the Special Issue Drug Resistance, Molecular Oncology and Genetics of Breast Cancer)
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.
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Keywords:
triple-negative breast cancer; PTEN; PI3K; mTOR; protein expression; gene deletions; multidrug resistance; ABCG2; ABCC1; ABCB1
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MDPI and ACS Style
Prvanović, M.; Nedeljković, M.; Tanić, N.; Tomić, T.; Terzić, T.; Milovanović, Z.; Maksimović, Z.; Tanić, N. Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer. Life 2021, 11, 1247. https://doi.org/10.3390/life11111247
AMA Style
Prvanović M, Nedeljković M, Tanić N, Tomić T, Terzić T, Milovanović Z, Maksimović Z, Tanić N. Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer. Life. 2021; 11(11):1247. https://doi.org/10.3390/life11111247
Chicago/Turabian StylePrvanović, Mirjana, Milica Nedeljković, Nasta Tanić, Tijana Tomić, Tanja Terzić, Zorka Milovanović, Zlatko Maksimović, and Nikola Tanić. 2021. "Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer" Life 11, no. 11: 1247. https://doi.org/10.3390/life11111247
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