Aberrant Promoter Methylation at CpG Cytosines Induce the Upregulation of the E2F5 Gene in Breast Cancer.
10.4048/jbc.2016.19.2.133
- Author:
Arshad ALI
1
;
Farman ULLAH
;
Irum Sabir ALI
;
Ahmad FARAZ
;
Mumtaz KHAN
;
Syed Tahir Ali SHAH
;
Nawab ALI
;
Muhammad SAEED
Author Information
1. Cancer Genetics and Epigenetics Lab, Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan. muhammad.saeed@comsats.edu.pk
- Publication Type:Original Article
- Keywords:
Breast neoplasms;
E2F5 transcription factor;
Methylation;
Promoter
- MeSH:
Biology;
Breast Neoplasms*;
Breast*;
Carcinogenesis;
Carcinoma, Ductal;
Carcinoma, Intraductal, Noninfiltrating;
Carcinoma, Lobular;
Cell Cycle;
Disease Progression;
DNA;
E2F5 Transcription Factor;
Epigenomics;
Eukaryotic Cells;
Genes, Regulator;
Humans;
Methylation*;
Polymerase Chain Reaction;
Promoter Regions, Genetic;
RNA, Messenger;
Up-Regulation*
- From:Journal of Breast Cancer
2016;19(2):133-141
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: The promoter methylation status of cell cycle regulatory genes plays a crucial role in the regulation of the eukaryotic cell cycle. CpG cytosines are actively subjected to methylation during tumorigenesis, resulting in gain/loss of function. E2F5 gene has growth repressive activities; various studies suggest its involvement in tumorigenesis. This study aims to investigate the epigenetic regulation of E2F5 in breast cancer to better understand tumor biology. METHODS: The promoter methylation status of 50 breast tumor tissues and adjacent normal control tissues was analyzed. mRNA expression was determined using SYBR® green quantitative polymerase chain reaction (PCR), and methylation-specific PCR was performed for bisulfite-modified genomic DNA using E2F5-specific primers to assess promoter methylation. Data was statistically analyzed. RESULTS: Significant (p<0.001) upregulation was observed in E2F5 expression among tumor tissues, relative to the control group. These samples were hypo-methylated at the E2F5 promoter region in the tumor tissues, compared to the control. Change in the methylation status (Δmeth) was significantly lower (p=0.022) in the tumor samples, indicating possible involvement in tumorigenesis. Patients at the postmenopausal stage showed higher methylation (75%) than those at the premenopausal stage (23.1%). Interestingly, methylation levels gradually increased from the early to the advanced stages of the disease (p<0.001), which suggests a putative role of E2F5 methylation in disease progression that can significantly modulate tumor biology at more advanced stage and at postmenopausal age (Pearson's r=0.99 and 0.86, respectively). Among tissues with different histological status, methylation frequency was higher in invasive lobular carcinoma (80.0%), followed by invasive ductal carcinoma (46.7%) and ductal carcinoma in situ (20.0%). CONCLUSION: Methylation is an important epigenetic factor that might be involved in the upregulation of E2F5 gene in tumor tissues, which can be used as a prognostic marker for breast cancer.
