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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2021
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oai:doaj.org-article:63084dd630e44de4a76874c2a02f3c442021-11-25T18:11:33ZRole of PTEN, PI3K, and mTOR in Triple-Negative Breast Cancer10.3390/life111112472075-1729https://doaj.org/article/63084dd630e44de4a76874c2a02f3c442021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1247https://doaj.org/toc/2075-1729Breast 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.Mirjana PrvanovićMilica NedeljkovićNasta TanićTijana TomićTanja TerzićZorka MilovanovićZlatko MaksimovićNikola TanićMDPI AGarticletriple-negative breast cancerPTENPI3KmTORprotein expressiongene deletionsScienceQENLife, Vol 11, Iss 1247, p 1247 (2021) |
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| collection |
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| language |
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| topic |
triple-negative breast cancer PTEN PI3K mTOR protein expression gene deletions Science Q |
| spellingShingle |
triple-negative breast cancer PTEN PI3K mTOR protein expression gene deletions Science Q 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 |
| 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. |
| format |
article |
| 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 |
| title |
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_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_sort |
role of pten, pi3k, and mtor in triple-negative breast cancer |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/63084dd630e44de4a76874c2a02f3c44 |
| work_keys_str_mv |
AT mirjanaprvanovic roleofptenpi3kandmtorintriplenegativebreastcancer AT milicanedeljkovic roleofptenpi3kandmtorintriplenegativebreastcancer AT nastatanic roleofptenpi3kandmtorintriplenegativebreastcancer AT tijanatomic roleofptenpi3kandmtorintriplenegativebreastcancer AT tanjaterzic roleofptenpi3kandmtorintriplenegativebreastcancer AT zorkamilovanovic roleofptenpi3kandmtorintriplenegativebreastcancer AT zlatkomaksimovic roleofptenpi3kandmtorintriplenegativebreastcancer AT nikolatanic roleofptenpi3kandmtorintriplenegativebreastcancer |
| _version_ |
1718411500457033728 |