Role of PTEN, PI3K, and mTOR in Triple-Negative 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 o...
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MDPI AG
2021-11-01
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| Online Access: | https://www.mdpi.com/2075-1729/11/11/1247 |
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| author | Mirjana Prvanović Milica Nedeljković Nasta Tanić Tijana Tomić Tanja Terzić Zorka Milovanović Zlatko Maksimović Nikola Tanić |
| author_facet | Mirjana Prvanović Milica Nedeljković Nasta Tanić Tijana Tomić Tanja Terzić Zorka Milovanović Zlatko Maksimović Nikola Tanić |
| author_sort | Mirjana Prvanović |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T05:20:41Z |
| format | Article |
| id | doaj.art-63084dd630e44de4a76874c2a02f3c44 |
| institution | Directory Open Access Journal |
| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-10T05:20:41Z |
| publishDate | 2021-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Life |
| spelling | doaj.art-63084dd630e44de4a76874c2a02f3c442023-11-23T00:05:04ZengMDPI AGLife2075-17292021-11-011111124710.3390/life11111247Role of PTEN, PI3K, and mTOR in Triple-Negative Breast CancerMirjana Prvanović0Milica Nedeljković1Nasta Tanić2Tijana Tomić3Tanja Terzić4Zorka Milovanović5Zlatko Maksimović6Nikola Tanić7Institute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11000 Belgrade, SerbiaDepartment of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences “Vinča”, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Radiobiology and Molecular Genetics, Institute of Nuclear Sciences “Vinča”, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaInstitute of Pathology, Faculty of Medicine, University of Belgrade, 11000 Belgrade, SerbiaDepartment of Pathology, Institute of Oncology and Radiology of Serbia, 11000 Belgrade, SerbiaPublic Health Institution Hospital “Sveti Vracevi”, 76300 Bijeljina, Republika Srpska, Bosnia and HerzegovinaDepartment of Neurobiology, Institute for Biological Research “Siniša Stanković”, National Institute of Republic of Serbia, University of Belgrade, 11000 Belgrade, SerbiaBreast 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.https://www.mdpi.com/2075-1729/11/11/1247triple-negative breast cancerPTENPI3KmTORprotein expressiongene deletions |
| spellingShingle | Mirjana Prvanović Milica Nedeljković Nasta Tanić Tijana Tomić Tanja Terzić Zorka Milovanović Zlatko Maksimović Nikola Tanić Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer Life triple-negative breast cancer PTEN PI3K mTOR protein expression gene deletions |
| title | Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer |
| title_full | Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer |
| title_fullStr | Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer |
| title_full_unstemmed | Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer |
| title_short | Role of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer |
| title_sort | role of pten pi3k and mtor in triple negative breast cancer |
| topic | triple-negative breast cancer PTEN PI3K mTOR protein expression gene deletions |
| url | https://www.mdpi.com/2075-1729/11/11/1247 |
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