Cellular senescence role in human pituitary neuroendocrine tumors
Cellular senescence emerges as an alternative response to stress. It is determined by cell arrest which allows cells to remain viable and to have an active metabolism. This barrier in tumorigenesis could explain the slow growth rate and benign characteristic of pituitary neuroendocrine tumors (...
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| Autores principales: | , , , , , , , |
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| Formato: | Artículo revista |
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Universidad Nacional Córdoba. Facultad de Ciencias Médicas. Secretaria de Ciencia y Tecnología
2022
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| Acceso en línea: | https://revistas.unc.edu.ar/index.php/med/article/view/39012 |
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| Sumario: | Cellular senescence emerges as an alternative response to stress. It is determined by cell arrest which allows cells to remain viable and to have an active metabolism. This barrier in tumorigenesis could explain the slow growth rate and benign characteristic of pituitary neuroendocrine tumors (PitNET). We aimed to establish senescence's contribution, particularly the reactive response to oxidative stress, in human somatotroph PitNet.
Paraffin-embedded PitNet samples were analyzed. These belonged to both female and male patients (n=9) and were supplied by Clínica Universitaria Reina Fabiola (REPIS 3974) and Sanatorio Allende (Córdoba). We were also provided with clinical records and immunolabeling data for growth hormone (GH) and Ki-67. The expression of 8-hydroxy-2'-deoxyguanosine (8OhdG), marker of oxidative damage in DNA, along with Nuclear factor erythroid 2-related factor 2 (Nrf2), which indicates activation of antioxidant response, was detected by immunohistochemistry. Five randomly chosen fields were selected (400x) and 1.000 cells were counted for every sample. Data is expressed as percentages of positive cells for nuclear 8OdHG in relation to the total number of cells. The intensity of cytoplasmic Nrf2 expression was classified as weak/strong and focal/diffuse regarding its distribution. Statics analysis: T-Test (p<0.05) for 8OhdG and Kruskal Wallis (p<0.05) for Nrf2.
In PiNet with Ki-67<3 (n=7) and densely granulated GH distribution (less aggressive) the percentage of positive cells for 8OdhG was 14,3%. In sparsely granulated tumors with Ki-67>3 (n=2) (more aggressive), the percentage for this marker was 9.28% (p>0.05). At the same time, in the first group Nrf2's expression was mainly focal and weak; while in the second group Nrf2's expression was diffuse and strong (p>0.05).
These results may suggest that in somatotroph PitNet an heterogeneous response to cell stress exists. The build-up of oxidative damage in DNA combined with a low antioxidant response could be the first signal to trigger senescence, which could explain the lower proliferative rate that these tumors have. Likewise, we speculate that higher expression of Nrf2 could counteract oxidative processes, enabling proliferation and promoting tumoral evolution.
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