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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.

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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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Results of ERβ staining in five consecutive trials. Human breast cancer sections immunostained for ERβ were subdivided using a scoring system for ERβ expression into negative (no staining), weak (<20% staining), low (21–40% staining), medium (41–60% staining), and high (>61% staining) expression. The percentage of sections in each expression level is indicated. The first two columns showed the results for all the fibroadenoma (column 1) and breast cancer (column 2) sections. The last three columns showed the results for all breast cancer sections in each of the genotypes of rs1271572.
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Figure 1: Results of ERβ staining in five consecutive trials. Human breast cancer sections immunostained for ERβ were subdivided using a scoring system for ERβ expression into negative (no staining), weak (<20% staining), low (21–40% staining), medium (41–60% staining), and high (>61% staining) expression. The percentage of sections in each expression level is indicated. The first two columns showed the results for all the fibroadenoma (column 1) and breast cancer (column 2) sections. The last three columns showed the results for all breast cancer sections in each of the genotypes of rs1271572.

Mentions: As shown in Figure 1, no or weak staining for ERβ was presented in less than 30% of fibroadenoma tissues, whereas it was observed in nearly 40% of the breast cancer tissues. Nearly 40% of the breast cancer tissues exhibited either no staining or weak staining for ERβ compared with < 30% for fibroadenoma tissues. Negative ERβ expression was more frequently observed in breast cancer patients (18.36%) than that in the fibroadenoma group (12.42%). Among the breast cancer patients with negative ERβ expression, the proportion of patients carrying the TT genotype (32.22%), was higher than that carrying the GG (14.63%) and GT (14.72%) subgroups combined (p < 0.05). Similarly, among breast cancer patients with weak ERβ expression, the proportion of patients carrying the TT genotypes of rs1271572 (31.78%) was higher than for the other subgroups, GG (21.97%) and GT (20.22%) (p < 0.05, Figure 1). Together, these results indicated that in the breast cancer patients, the TT genotype of rs1271572 was strongly associated with negative or weak ERβ gene expression. Expression of ERβ was determined using immunohistochemical staining. Representative staining images with different scores were shown in Figure 2.


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)

Results of ERβ staining in five consecutive trials. Human breast cancer sections immunostained for ERβ were subdivided using a scoring system for ERβ expression into negative (no staining), weak (<20% staining), low (21–40% staining), medium (41–60% staining), and high (>61% staining) expression. The percentage of sections in each expression level is indicated. The first two columns showed the results for all the fibroadenoma (column 1) and breast cancer (column 2) sections. The last three columns showed the results for all breast cancer sections in each of the genotypes of rs1271572.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Results of ERβ staining in five consecutive trials. Human breast cancer sections immunostained for ERβ were subdivided using a scoring system for ERβ expression into negative (no staining), weak (<20% staining), low (21–40% staining), medium (41–60% staining), and high (>61% staining) expression. The percentage of sections in each expression level is indicated. The first two columns showed the results for all the fibroadenoma (column 1) and breast cancer (column 2) sections. The last three columns showed the results for all breast cancer sections in each of the genotypes of rs1271572.
Mentions: As shown in Figure 1, no or weak staining for ERβ was presented in less than 30% of fibroadenoma tissues, whereas it was observed in nearly 40% of the breast cancer tissues. Nearly 40% of the breast cancer tissues exhibited either no staining or weak staining for ERβ compared with < 30% for fibroadenoma tissues. Negative ERβ expression was more frequently observed in breast cancer patients (18.36%) than that in the fibroadenoma group (12.42%). Among the breast cancer patients with negative ERβ expression, the proportion of patients carrying the TT genotype (32.22%), was higher than that carrying the GG (14.63%) and GT (14.72%) subgroups combined (p < 0.05). Similarly, among breast cancer patients with weak ERβ expression, the proportion of patients carrying the TT genotypes of rs1271572 (31.78%) was higher than for the other subgroups, GG (21.97%) and GT (20.22%) (p < 0.05, Figure 1). Together, these results indicated that in the breast cancer patients, the TT genotype of rs1271572 was strongly associated with negative or weak ERβ gene expression. Expression of ERβ was determined using immunohistochemical staining. Representative staining images with different scores were shown in Figure 2.

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