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Significance of rs1271572 in the estrogen receptor beta gene promoter and its correlation with breast cancer in a southwestern Chinese population.

Chen L, Liang Y, Qiu J, Zhang L, Chen X, Luo X, Jiang J - J. Biomed. Sci. (2013)

Bottom Line: The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene.Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: To characterize single nucleotide polymorphisms (SNPs) within the promoter region of the estrogen receptor beta (ERβ) gene and to analyze the association of ERβ SNPs with susceptibility to breast cancer. Genotype frequencies of five SNPs (rs3020449, rs3020450, rs2987983, rs1271572 and rs1887994) in the promoter region of the ERβ gene in 873 women with breast cancer, 645 women with fibroadenoma and 700 healthy women were determined using an allele-specific tetra-primer polymerase chain reaction (PCR). Kaplan-Meier survival analysis was performed to evaluate the association of selected rs1271572 with prognosis in breast cancer. Electrophoretic mobility-shift assays were conducted to explore the binding of SNP rs1271572 containing probes to transcriptional factor Ying Yang 1 (YY1).

Results: Women with the homozygous TT genotype of rs1271572 had a significantly higher risk in developing breast cancer. Breast cancer patients with the TT genotype of rs1271572 had lower five-year survival rates than those with other genotypes and were more likely to suffer brain metastases. The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.

Conclusions: TT genotype of rs1271572 is associated with increased risk for breast cancer in Chinese women and is associated with unfavored prognosis in Chinese breast cancer patients. TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene. Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.

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Prediction of TF binding sites in the different alleles of rs1271572. The results from the TFSEARCH (http://www.cbrc.jp/research/db/TFSEARCH.html) prediction of transcription factor binding sites in the ERβ promoter were shown. The T allele of rs1271572 resulted in the loss of the Yin Yang 1 (YY1) transcription factor binding site.
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Figure 4: Prediction of TF binding sites in the different alleles of rs1271572. The results from the TFSEARCH (http://www.cbrc.jp/research/db/TFSEARCH.html) prediction of transcription factor binding sites in the ERβ promoter were shown. The T allele of rs1271572 resulted in the loss of the Yin Yang 1 (YY1) transcription factor binding site.

Mentions: Transcription of the human ERβ gene occurs from at least two different promoters, promoter 0 N and promoter 0 K, with promoter 0 N being more prominent in breast epithelial cells and breast cancer cells[15][16]. As the TT genotype of rs1271572 is significantly associated with low ERβ expression in breast cancer patients (Figure 1), we hypothesized that certain transcriptional factors (TFs) that are critical to regulate ERβ expression specifically bind to G allele, but not T allele containing promoters. To search for TFs that differently bind to these promoters, bioinformatics approaches (http://www.cbrc.jp/research/db/TFSEARCH.html; http://variome.kobic.re.kr/SNPatPromoter/) were used which showed that the rs1271572 T allele could result in the loss of the Yin Yang 1 (YY1) transcription factor binding (Figure 4). We speculated that the loss of the YY1 binding site might be involved in the decreased expression of the ERβ gene.


Significance of rs1271572 in the estrogen receptor beta gene promoter and its correlation with breast cancer in a southwestern Chinese population.

Chen L, Liang Y, Qiu J, Zhang L, Chen X, Luo X, Jiang J - J. Biomed. Sci. (2013)

Prediction of TF binding sites in the different alleles of rs1271572. The results from the TFSEARCH (http://www.cbrc.jp/research/db/TFSEARCH.html) prediction of transcription factor binding sites in the ERβ promoter were shown. The T allele of rs1271572 resulted in the loss of the Yin Yang 1 (YY1) transcription factor binding site.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3672062&req=5

Figure 4: Prediction of TF binding sites in the different alleles of rs1271572. The results from the TFSEARCH (http://www.cbrc.jp/research/db/TFSEARCH.html) prediction of transcription factor binding sites in the ERβ promoter were shown. The T allele of rs1271572 resulted in the loss of the Yin Yang 1 (YY1) transcription factor binding site.
Mentions: Transcription of the human ERβ gene occurs from at least two different promoters, promoter 0 N and promoter 0 K, with promoter 0 N being more prominent in breast epithelial cells and breast cancer cells[15][16]. As the TT genotype of rs1271572 is significantly associated with low ERβ expression in breast cancer patients (Figure 1), we hypothesized that certain transcriptional factors (TFs) that are critical to regulate ERβ expression specifically bind to G allele, but not T allele containing promoters. To search for TFs that differently bind to these promoters, bioinformatics approaches (http://www.cbrc.jp/research/db/TFSEARCH.html; http://variome.kobic.re.kr/SNPatPromoter/) were used which showed that the rs1271572 T allele could result in the loss of the Yin Yang 1 (YY1) transcription factor binding (Figure 4). We speculated that the loss of the YY1 binding site might be involved in the decreased expression of the ERβ gene.

Bottom Line: The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene.Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: To characterize single nucleotide polymorphisms (SNPs) within the promoter region of the estrogen receptor beta (ERβ) gene and to analyze the association of ERβ SNPs with susceptibility to breast cancer. Genotype frequencies of five SNPs (rs3020449, rs3020450, rs2987983, rs1271572 and rs1887994) in the promoter region of the ERβ gene in 873 women with breast cancer, 645 women with fibroadenoma and 700 healthy women were determined using an allele-specific tetra-primer polymerase chain reaction (PCR). Kaplan-Meier survival analysis was performed to evaluate the association of selected rs1271572 with prognosis in breast cancer. Electrophoretic mobility-shift assays were conducted to explore the binding of SNP rs1271572 containing probes to transcriptional factor Ying Yang 1 (YY1).

Results: Women with the homozygous TT genotype of rs1271572 had a significantly higher risk in developing breast cancer. Breast cancer patients with the TT genotype of rs1271572 had lower five-year survival rates than those with other genotypes and were more likely to suffer brain metastases. The rs1271572 G→T SNP abrogated YY1 binding and reduced the transcription activity of the promoter 0 N in the ERβ gene in vitro.

Conclusions: TT genotype of rs1271572 is associated with increased risk for breast cancer in Chinese women and is associated with unfavored prognosis in Chinese breast cancer patients. TT genotype of rs1271572 inhibited expression of ERβ gene by down regulating transcriptional activity of the promoter 0 N in the ERβ gene. Our data revealed that the TT genotype of rs1271572 resulted in loss of the YY1 binding site and reduced the transcription activity of the promoter 0 N in the ERβ gene.

Show MeSH
Related in: MedlinePlus