Hjem Publikasjoner Mutations in TP53 increase the risk of SO[...]

Mutations in TP53 increase the risk of SOX2 copy number alterations and silencing of TP53 reduces SOX2 expression in non-small cell lung cancer

Background: Amplifications of the transcription factor, SRY (sex determining region Y)-box 2 (SOX2), are common in non-small cell lung cancer (NSCLC). SOX2 signaling is important in maintaining the stem cell-like phenotype of cancer cells and contributes to the pathogenesis of lung cancer. TP53 is known to inhibit gene amplifications and to repress many stem cell-associated genes following DNA damage. The aim of this study was to investigate if TP53 mutational status affected SOX2 copy number variation and gene expression in early-stage NSCLC patients; moreover, to assess if TP53 regulates SOX2 expression in human lung cancer cells. Methods: 258 early-stage lung cancer patients were included in the study. Exons 4–9 in the TP53 gene were sequenced for mutations in tumor tissues. SOX2 copy number as well as TP53 and SOX2 gene expression were analyzed in tumor and in adjacent non-tumorous tissues by qPCR. TP53 and SOX2 were silenced using gene-specific siRNAs in human lung adenocarcinoma A427 cells, and the expression of TP53, SOX2 and subset of selected miRNAs was analyzed by qPCR. The odds ratios (ORs) for associations between copy number variation and lung cancer were estimated by conditional logistic regression, and the correlation between gene status and clinicopathological characteristics was...

Samulin-Erdem, Johanna Maria; Skaug, Vidar; Bakke, Per S.; Gulsvik, Amund; Haugen, Aage; Zienolddiny, Shanbeh
BMC Cancer 16(1)
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