p53 Stabilization Induces Cell Growth Inhibition and Affects IGF2 Pathway in Response to Radiotherapy in Adrenocortical Cancer Cells
| العنوان: | p53 Stabilization Induces Cell Growth Inhibition and Affects IGF2 Pathway in Response to Radiotherapy in Adrenocortical Cancer Cells |
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| المؤلفون: | Randa El Gawhary, Barbara Bucci, Antonio Stigliano, Donatella Amendola, Vincenzo Toscano, Silvia Misiti, Camilla Sampaoli, Lidia Cerquetti, Rodolfo Marchese, Giuseppe Novelli |
| المصدر: | PLoS ONE, Vol 7, Iss 9, p e45129 (2012) PLoS ONE |
| بيانات النشر: | PUBLIC LIBRARY SCIENCE, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Programmed cell death, Somatic cell, Molecular Sequence Data, Cell, lcsh:Medicine, Biology, Endocrinology, Diagnostic Medicine, Insulin-Like Growth Factor II, Cell Line, Tumor, Radiation, Ionizing, Molecular Cell Biology, Pathology, Adrenocortical Carcinoma, In Situ Nick-End Labeling, medicine, Humans, Adrenocortical carcinoma, Amino Acid Sequence, RNA, Messenger, lcsh:Science, Protein kinase B, Cell Proliferation, Multidisciplinary, Cell Death, Radiotherapy, Base Sequence, Protein Stability, Cell growth, lcsh:R, Sequence Analysis, DNA, medicine.disease, Molecular biology, Enzyme Activation, Gene Expression Regulation, Neoplastic, medicine.anatomical_structure, Oncology, Cell culture, Adrenal Cortex, Medicine, lcsh:Q, Tumor Suppressor Protein p53, Signal transduction, Proto-Oncogene Proteins c-akt, Biomarkers, Research Article, General Pathology, Signal Transduction |
| الوصف: | Adrenocortical carcinoma (ACC) is a very rare endocrine tumour, with variable prognosis, depending on tumour stage and time of diagnosis. However, it is generally fatal, with an overall survival of 5 years from detection. Radiotherapy usefulness for ACC treatment has been widely debated and seems to be dependent on molecular alterations, which in turn lead to increased radio-resistance. Many studies have shown that p53 loss is an important risk factor for malignant adrenocortical tumour onset and it has been reported that somatic mutations in TP53 gene occur in 27 to 70% of adult sporadic ACCs. In this study, we investigated the role of somatic mutations of the TP53 gene in response to ionizing radiation (IR). We studied the status of p53 in two adrenocortical cell lines, H295R and SW-13, harbouring non-functioning forms of this protein, owing to the lack of exons 8 and 9 and a point mutation in exon 6, respectively. Moreover, these cell lines show high levels of p-Akt and IGF2, especially H295R. We noticed that restoration of p53 activity led to inhibition of growth after transient transfection of cells with wild type p53. Evaluation of their response to IR in terms of cell proliferation and viability was determined by means of cell count and TUNEL assay.(wt)p53 over-expression also increased cell death by apoptosis following radiation in both cell lines. Moreover, RT-PCR and Western blotting analysis of some p53 target genes, such as BCL2, IGF2 and Akt demonstrated that p53 activation following IR led to a decrease in IGF2 expression. This was associated with a reduction in the active form of Akt. Taken together, these results highlight the role of p53 in response to radiation of ACC cell lines, suggesting its importance as a predictive factor for radiotherapy in malignant adrenocortical tumours cases. |
| اللغة: | English |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e213bff36334cd0bfdd4481a57355d13Test http://hdl.handle.net/11573/493473Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e213bff36334cd0bfdd4481a57355d13 |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |