Aberrant promoter methylation status is associated with upregulation of the E2F4 gene in breast cancer

Farman,Farman  Ullah; Haq,Farhan; Muhammad,Noor; Ali,Nawab; Rahman,Hazir; Saeed,Muhammad

doi:10.3892/ol.2018.8382

Aberrant promoter methylation status is associated with upregulation of the E2F4 gene in breast cancer

Authors:
- Farman Ullah Farman
- Farhan Haq
- Noor Muhammad
- Nawab Ali
- Hazir Rahman
- Muhammad Saeed
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Affiliations: Cancer Genetics and Epigenetics Laboratory, Department of Biosciences, COMSATS Institute of Information Technology, Chak Shahzad, Islamabad 45550, Pakistan, Department of Biotechnology and Genetic Engineering, Kohat University of Science and Technology, Kohat 26000, Pakistan, Department of Microbiology, Abdul Wali Khan University Mardan, Khyber Pakhtunkhwa 23200, Pakistan
Published online on: March 29, 2018 https://doi.org/10.3892/ol.2018.8382
Pages: 8461-8469
Copyright: © Farman et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

E2F4 is an important basal transcription factor with the potential to promote tumor growth. Its upregulation in various types of cancer has been linked to numerous genetic factors; however, the nature of the involvement of epigenetic mechanisms, including DNA methylation, remains elusive. In the present study, E2F4 expression profiles were determined in 100 paired breast tumor and control samples, through RT‑qPCR using the SYBR® green method. Furthermore, the E2F4 promoter methylation status in each of these samples was assessed using methylation specific PCR, in order to evaluate its impact on gene expression. A two‑fold increase in E2F4 gene expression was observed in the breast tumors compared with in their respective controls (P=0.022); of these tumors, ~72% were under‑methylated. The change in methylation status was also significantly higher (P<0.001) in the tumor samples. Methylation status was negatively correlated (r=‑30) with E2F4 expression profiles, indicating that a decrease in methylation may promote higher expression of E2F4. The two study cohorts (>45 and ≤45 years) had comparable methylation profiles, though they had significantly decreased methylation status compared with controls. Various histo‑pathological types also have different methylation profiles, indicating the presence of a tissue specific methylation signature. The results of the present study demonstrated that E2F4 methylation status can have a notable influence on its expression, and that it may have prognostic value in breast carcinogenesis.

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