p53 Stabilization Induces Cell Growth Inhibition and Affects IGF2 Pathway in Response to Radiotherapy in Adrenocortical Cancer Cells

Camilla Sampaoli, Lidia Cerquetti, Randa El Gawhary, Barbara Bucci, Donatella Amendola, Rodolfo Marchese, Silvia Misiti, Giuseppe Novelli, Vincenzo Toscano, Antonio Stigliano

Research output: Contribution to journalArticle

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Abstract

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.wtp53 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.

Original languageEnglish
Article numbere45129
JournalPLoS One
Volume7
Issue number9
DOIs
Publication statusPublished - Sep 19 2012

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Adrenal Cortex Neoplasms
Radiotherapy
Cell growth
radiotherapy
Adrenocortical Carcinoma
growth retardation
Tumors
cell growth
Ionizing radiation
p53 Genes
Stabilization
Ionizing Radiation
ionizing radiation
Cells
cell lines
carcinoma
Cell Line
somatic mutation
neoplasms
Genes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Sampaoli, C., Cerquetti, L., Gawhary, R. E., Bucci, B., Amendola, D., Marchese, R., ... Stigliano, A. (2012). p53 Stabilization Induces Cell Growth Inhibition and Affects IGF2 Pathway in Response to Radiotherapy in Adrenocortical Cancer Cells. PLoS One, 7(9), [e45129]. https://doi.org/10.1371/journal.pone.0045129

p53 Stabilization Induces Cell Growth Inhibition and Affects IGF2 Pathway in Response to Radiotherapy in Adrenocortical Cancer Cells. / Sampaoli, Camilla; Cerquetti, Lidia; Gawhary, Randa El; Bucci, Barbara; Amendola, Donatella; Marchese, Rodolfo; Misiti, Silvia; Novelli, Giuseppe; Toscano, Vincenzo; Stigliano, Antonio.

In: PLoS One, Vol. 7, No. 9, e45129, 19.09.2012.

Research output: Contribution to journalArticle

Sampaoli, C, Cerquetti, L, Gawhary, RE, Bucci, B, Amendola, D, Marchese, R, Misiti, S, Novelli, G, Toscano, V & Stigliano, A 2012, 'p53 Stabilization Induces Cell Growth Inhibition and Affects IGF2 Pathway in Response to Radiotherapy in Adrenocortical Cancer Cells', PLoS One, vol. 7, no. 9, e45129. https://doi.org/10.1371/journal.pone.0045129
Sampaoli, Camilla ; Cerquetti, Lidia ; Gawhary, Randa El ; Bucci, Barbara ; Amendola, Donatella ; Marchese, Rodolfo ; Misiti, Silvia ; Novelli, Giuseppe ; Toscano, Vincenzo ; Stigliano, Antonio. / p53 Stabilization Induces Cell Growth Inhibition and Affects IGF2 Pathway in Response to Radiotherapy in Adrenocortical Cancer Cells. In: PLoS One. 2012 ; Vol. 7, No. 9.
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