Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cells
The Notch-3 receptor is a recognized key regulator of vascular responses and is increasingly associated with tumorigenesis. Hypoxia-inducible factors activate specific signaling pathways such as Notch in a number of cellular models. This study aimed to evaluate the regulation of Notch-3 by hypoxia i...
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| Format: | Article |
| Language: | English |
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Elsevier
2016-05-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844015305442 |
| _version_ | 1818258585547702272 |
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| author | Armelle Meunier Angela Nilda Flores Niamh McDermott Karla Rivera-Figueroa Antoinette Perry Thomas Lynch Kathrine Røe Redalen Laure Marignol |
| author_facet | Armelle Meunier Angela Nilda Flores Niamh McDermott Karla Rivera-Figueroa Antoinette Perry Thomas Lynch Kathrine Røe Redalen Laure Marignol |
| author_sort | Armelle Meunier |
| collection | DOAJ |
| description | The Notch-3 receptor is a recognized key regulator of vascular responses and is increasingly associated with tumorigenesis. Hypoxia-inducible factors activate specific signaling pathways such as Notch in a number of cellular models. This study aimed to evaluate the regulation of Notch-3 by hypoxia in prostate cancer cells. Notch-3 gene and protein expression was established in a panel of aerobic and hypoxic prostate cell lines in vitro, the CWR22 xenograft model and RNA extracted from low grade (Gleason score < = 6); high grade (Gleason score > = 7); non-hypoxic (low HIF, low VEGF); hypoxic (high HIF, high VEGF) patient FFPE specimens. NOTCH-3 was upregulated in PC3 (3-fold), 22Rv1 (4.1-fold) and DU145 (3.8-fold) but downregulated in LnCaP (12-fold) compared to the normal cell lines. NOTCH-3 expression was modified following hypoxic exposure in these cells. NOTCH-3 was upregulated (2.2-fold) in higher grade and hypoxic tumors, when compared to benign and aerobic pools. In the CWR22 xenograft model, Notch-3 expression was restored in castrate resistant tumors. Nuclear translocation of the Notch-3 intracellular domain was no longer detected following exposure of cells to hypoxia but not associated with a change in expression of HES-1. Our data further identifies Notch-3 as a potentially key hypoxic-responsive member of the Notch pathway in prostate tumorigenesis. |
| first_indexed | 2024-12-12T18:01:53Z |
| format | Article |
| id | doaj.art-34d93241a27f457a80894a714cec7bae |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-12-12T18:01:53Z |
| publishDate | 2016-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-34d93241a27f457a80894a714cec7bae2022-12-22T00:16:36ZengElsevierHeliyon2405-84402016-05-012510.1016/j.heliyon.2016.e00104Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cellsArmelle Meunier0Angela Nilda Flores1Niamh McDermott2Karla Rivera-Figueroa3Antoinette Perry4Thomas Lynch5Kathrine Røe Redalen6Laure Marignol7Radiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Trinity College Dublin, IrelandDivision of International Health, Mount Sinai School of Medicine, New York, USARadiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Trinity College Dublin, IrelandDivision of International Health, Mount Sinai School of Medicine, New York, USACancer Biology and Therapeutics Laboratory, Conway Institute, University College Dublin, IrelandDepartment of Urology, St James’s Hospital, Dublin 8, IrelandDepartment of Oncology, Akershus University Hospital, Lørenskog, NorwayRadiobiology and Molecular Oncology, Applied Radiation Therapy Trinity, Trinity College Dublin, IrelandThe Notch-3 receptor is a recognized key regulator of vascular responses and is increasingly associated with tumorigenesis. Hypoxia-inducible factors activate specific signaling pathways such as Notch in a number of cellular models. This study aimed to evaluate the regulation of Notch-3 by hypoxia in prostate cancer cells. Notch-3 gene and protein expression was established in a panel of aerobic and hypoxic prostate cell lines in vitro, the CWR22 xenograft model and RNA extracted from low grade (Gleason score < = 6); high grade (Gleason score > = 7); non-hypoxic (low HIF, low VEGF); hypoxic (high HIF, high VEGF) patient FFPE specimens. NOTCH-3 was upregulated in PC3 (3-fold), 22Rv1 (4.1-fold) and DU145 (3.8-fold) but downregulated in LnCaP (12-fold) compared to the normal cell lines. NOTCH-3 expression was modified following hypoxic exposure in these cells. NOTCH-3 was upregulated (2.2-fold) in higher grade and hypoxic tumors, when compared to benign and aerobic pools. In the CWR22 xenograft model, Notch-3 expression was restored in castrate resistant tumors. Nuclear translocation of the Notch-3 intracellular domain was no longer detected following exposure of cells to hypoxia but not associated with a change in expression of HES-1. Our data further identifies Notch-3 as a potentially key hypoxic-responsive member of the Notch pathway in prostate tumorigenesis.http://www.sciencedirect.com/science/article/pii/S2405844015305442MedicineCell biology |
| spellingShingle | Armelle Meunier Angela Nilda Flores Niamh McDermott Karla Rivera-Figueroa Antoinette Perry Thomas Lynch Kathrine Røe Redalen Laure Marignol Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cells Heliyon Medicine Cell biology |
| title | Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cells |
| title_full | Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cells |
| title_fullStr | Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cells |
| title_full_unstemmed | Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cells |
| title_short | Hypoxia regulates Notch-3 mRNA and receptor activation in prostate cancer cells |
| title_sort | hypoxia regulates notch 3 mrna and receptor activation in prostate cancer cells |
| topic | Medicine Cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S2405844015305442 |
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