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Published on: August 12, 2015
RhoBTB2 gene in breast cancer is silenced by promoter methylation
Weiwei Tang1, Chuan Wang1, Fangmeng Fu2
1Department of Oncology, Graduate School of Education, Fujian Medical University, Fuzhou, Fujian, P.R. China.
Abstract:
Mutation analysis in breast cancer has failed to explain the inactivation of RhoBTB2, a candidate breast cancer tumor suppressor gene on chromosome 8p. Some breast cancer-related genes in this region become inactivated by hypermethylation, and hypermethylation of RhoBTB2 abrogates its expression in bladder cancers. The aim of the present study was to determine whether RhoBTB2 was silenced by methylation in breast cancer. Nested methylation-specific PCR (nMSP) and quantitative reverse transcription PCR were used to analyze the methylation status and mRNA levels of RhoBTB2 in 50 paired breast cancer and normal tissues and the results were correlated with clinicopathological characteristics. Promoter methylation and the downregulation of RhoBTB2 mRNA was observed in tumor tissues (P<0.001). mRNA levels were decreased in samples with methylation (χ² = 15.751, P<0.001). RhoBTB2 methylation was observed preferentially in progesterone receptor (PR)-negative samples (P<0.05). The results demonstrated that aberrant methylation of RhoBTB2 may be responsible for the suppression of RhoBTB2 mRNA expression in breast cancer, a significant event during the genesis of breast cancer that correlated with PR status.
Insights
Aberrant methylation silences the RhoBTB2 tumor suppressor gene in breast cancer, leading to decreased mRNA expression. This methylation is linked to progesterone receptor-negative status, suggesting a role in breast cancer development.
Area of Science:
- Oncology
- Molecular Biology
- Epigenetics
Background:
- RhoBTB2 is a candidate tumor suppressor gene on chromosome 8p implicated in breast cancer.
- Previous studies show RhoBTB2 inactivation is not explained by mutation and is silenced by hypermethylation in bladder cancer.
Purpose of the Study:
- To investigate if RhoBTB2 is silenced by promoter methylation in breast cancer.
- To correlate RhoBTB2 methylation status with its mRNA expression and clinicopathological features.
Main Methods:
- Nested methylation-specific PCR (nMSP) to assess RhoBTB2 promoter methylation.
- Quantitative reverse transcription PCR to measure RhoBTB2 mRNA levels.
- Analysis of 50 paired breast cancer and normal tissue samples.
Main Results:
- RhoBTB2 promoter methylation and decreased mRNA expression were significantly observed in breast tumor tissues compared to normal tissues (P<0.001).
- RhoBTB2 mRNA levels were significantly lower in methylated samples (P<0.001).
- Methylation was preferentially detected in progesterone receptor (PR)-negative breast cancer samples (P<0.05).
Conclusions:
- Aberrant methylation of RhoBTB2 is a key mechanism for its mRNA expression suppression in breast cancer.
- RhoBTB2 silencing via methylation is a significant event in breast cancer genesis.
- RhoBTB2 methylation status correlates with PR negativity, indicating a potential role in specific breast cancer subtypes.
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