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Genetic and Epigenetic Silencing of the Beclin 1 Gene in Sporadic Breast Tumors

Overview
Journal BMC Cancer
Publisher Biomed Central
Specialty Oncology
Date 2010 Mar 17
PMID 20230646
Citations 63
Authors
Affiliations
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Abstract

Background: Beclin 1, an important autophagy-related protein in human cells, is involved in cell death and cell survival. Beclin 1 mapped to human chromosome 17q21. It is widely expressed in normal mammary epithelial cells. Although down-regulated expression with mono-allelic deletions of beclin 1 gene was frequently observed in breast tumors, whether there was other regulatory mechanism of beclin 1 was to be investigated. We studied the expression of beclin 1 and explored the possible regulatory mechanisms on its expression in breast tumors.

Methods: 20 pairs of tumors and adjacent normal tissues from patients with sporadic breast invasive ductal cancer (IDCs) were collected. The mRNA expression of beclin 1 was detected by real-time quantitative RT-PCR. Loss of heterozygosity (LOH) was determined by real-time quantitative PCR and microsatellite methods. The protein expression of beclin 1, p53, BRCA1 and BRCA2 was assessed by immunohistochemistry. CpG islands in 5' genomic region of beclin 1 gene were identified using MethylPrimer Program. Sodium bisulfite sequencing was used in examining the methylation status of each CpG island.

Results: Decreased beclin 1 mRNA expression was detected in 70% of the breast tumors, and the protein levels were co-related to the mRNA levels. Expression of beclin 1 mRNA was demonstrated to be much higher in the BRCA1 positive tumors than that in the BRCA1 negative ones. Loss of heterozygosity was detected in more than 45% of the breast tumors, and a dense cluster of CpG islands was found from the 5' end to the intron 2 of the beclin 1 gene. Methylation analysis showed that the promoter and the intron 2 of beclin 1 were aberrantly methylated in the tumors with decreased expression.

Conclusions: These data indicated that LOH and aberrant DNA methylation might be the possible reasons of the decreased expression of beclin 1 in the breast tumors. The findings here shed some new light on the regulatory mechanisms of beclin 1 in breast cancer.

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References
1.
Dobrovic A, Simpfendorfer D . Methylation of the BRCA1 gene in sporadic breast cancer. Cancer Res. 1997; 57(16):3347-50. View

2.
Thor A, Moore DH I, Edgerton S, Kawasaki E, Reihsaus E, Lynch H . Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst. 1992; 84(11):845-55. DOI: 10.1093/jnci/84.11.845. View

3.
Welcsh P, OWENS K, King M . Insights into the functions of BRCA1 and BRCA2. Trends Genet. 2000; 16(2):69-74. DOI: 10.1016/s0168-9525(99)01930-7. View

4.
Gowen L, Avrutskaya A, Latour A, Koller B, Leadon S . BRCA1 required for transcription-coupled repair of oxidative DNA damage. Science. 1998; 281(5379):1009-12. DOI: 10.1126/science.281.5379.1009. View

5.
Furuya D, Tsuji N, Yagihashi A, Watanabe N . Beclin 1 augmented cis-diamminedichloroplatinum induced apoptosis via enhancing caspase-9 activity. Exp Cell Res. 2005; 307(1):26-40. DOI: 10.1016/j.yexcr.2005.02.023. View