BRCA1 Expression Status in Relation to DNA Methylation of the BRCA1 Promoter Region in Sporadic Breast Cancers
BRCA1 Expression Status in Relation to DNA Methylation of the BRCA1 Promoter Region in Sporadic Breast Cancers
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散发性乳腺癌中 BRCA1 表达状态与 BRCA1 启动子区域 DNA 甲基化相关
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
T. Nakajima
中科院分区：
文献类型：
--
作者：
Y. Niwa;T. Oyama;T. Nakajima
为了了解BRCA 1在散发性乳腺癌中的生物学作用，我们采用分子生物学和免疫组化方法研究了BRCA 1启动子区DNA甲基化与BRCA 1表达之间的关系。此外，BRCA1表达与各种细胞周期调控蛋白的表达和癌细胞的形态核分级进行了比较。在这项研究中调查的32例散发性乳腺癌中，10例（31%）显示BRCA1启动子区域的DNA甲基化。BRCA 1表达于癌细胞核，32例癌中18例（56%）BRCA 1阳性。BRCA1甲基化的乳腺癌缺乏BRCA1表达，只有三种癌症除外，并且在散发性乳腺癌中BRCA1甲基化与其表达之间存在显著的负相关关系（P=0.043）。与各种细胞周期调控蛋白的表达相比，BRCA 1甲基化的乳腺癌中雌激素受体（ER）和p27表达降低（P =0.016和0.018），p21表达升高（P=0.011）。此外，没有BRCA 1表达或BRCA 1甲基化的乳腺癌倾向于包含更高级别的细胞核。这些结果表明，BRCA 1甲基化可能对其表达有很大影响，BRCA 1表达可能在细胞周期调控中起重要作用，并影响散发性乳腺癌的恶性程度。
To understand the biological role of BRCA1 in sporadic breast cancers, the relationship between DNA methylation of the BRCA1 Promoter region and BRCA1 expression was studied using molecular biological and immunohistochemical methods. Furthermore, BRCA1 expression was compared with the expression of various cell cycle regulatory proteins and the morphological nuclear grade of cancer cells. Of 32 sporadic breast cancers investigated in this study, 10 (31%) revealed DNA methylation of the BRCA1 promoter region. The expression of BRCA1 was observed in the nuclei of cancer cells and 18 (56%) of 32 cancers were positive for BRCA1 immunoreactivity. Breast cancers with BRCA1 methylation lacked BRCA1 expression, except for only three cancers, and there was a significant inverse relationship between BRCA1 methylation and its expression in sporadic breast cancers (P=0.043). Compared with the expression of various cell cycle regulatory proteins, breast cancers with BRCA1 methylation showed decreased expression of estrogen receptor (P=0.016) and p27 (P=0.018) and increased expression of p21 (P=0.011). Furthermore, breast cancers without BRCA1 expression or with BRCA1 methylation had a tendency to contain nuclei with higher grade. These findings indicate that BRCA1 methylation might greatly influence its expression and BRCA1 expression might play an important role in cell cycle regulation and influence the grade of malignancy of sporadic breast cancers.
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影响因子：
56.9
作者：
FUTREAL, PA;LIU, QY;WISEMAN, R
通讯作者：
WISEMAN, R
DOI：
10.1073/pnas.91.21.9700
发表时间：
1994-10-11
影响因子：
11.1
作者：
HERMAN, JG;LATIF, F;BAYLIN, SB
通讯作者：
BAYLIN, SB
影响因子：
11.2
作者：
James G. Herman;J. Jen;A. Merlo;S. Baylin
通讯作者：
James G. Herman;J. Jen;A. Merlo;S. Baylin
影响因子：
56.9
作者：
MIKI, Y;SWENSEN, J;SKOLNICK, MH
通讯作者：
SKOLNICK, MH
人类前列腺癌中 CD44 转移抑制基因的甲基化。
影响因子：
11.2
作者：
Lou,W;Krill,D;Dhir,R;Becich,MJ;Dong,JT;FriersonJr,HF;Isaacs,WB;Isaacs,JT;Gao,AC
通讯作者：
Gao,AC