Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas.
Serum estradiol levels associated with specific gene expression patterns in normal breast tissue and in breast carcinomas.
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DOI：
10.1186/1471-2407-11-332
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发表时间：
2011-08-03
期刊：
影响因子：
3.8
通讯作者：
Helland Å
中科院分区：
文献类型：
--
作者：
Haakensen VD;Bjøro T;Lüders T;Riis M;Bukholm IK;Kristensen VN;Troester MA;Homen MM;Ursin G;Børresen-Dale AL;Helland Å
高血清雌二醇水平与绝经后乳腺癌风险增加相关。关于正常乳腺组织中的基因表达与循环血清雌二醇水平的关系知之甚少。我们使用 79 名健康女性和 64 名乳腺癌患者的数据将乳腺组织样本的全基因组表达数据与血清激素水平进行了比较。微阵列显着性分析（SAM）用于识别差异表达基因，多元线性回归用于识别独立关联。发现 6 个基因（SCGB3A1、RSPO1、TLN2、SLITRK4、DCLK1、PTGS1）根据血清雌二醇水平存在差异表达（FDR = 0）。其中三个独立预测多变量模型中的雌二醇水平，因为在血清雌二醇高的女性的乳房样本中，SCGB3A1 (HIN1) 和 TLN2 上调，PTGS1 (COX1) 下调。血清雌二醇，但没有一个差异表达基因与乳房X光密度（另一个重要的乳腺癌危险因素）显着相关。在乳腺癌中，GREB1 和 AREG 的表达与所有癌症和雌激素受体阳性病例亚组中的血清雌二醇相关。我们已经鉴定出与正常乳腺组织和乳腺癌中血清雌二醇水平相关的基因。 SCGB3A1 是一种被认为是抑癌基因，可抑制细胞生长和侵袭，并且在许多上皮癌中被甲基化和下调。我们的研究结果表明，该基因是雌二醇水平较高的健康女性乳腺细胞增殖的重要抑制剂。在乳房中，该基因仅在管腔细胞中表达，并且在非 BRCA 相关乳腺癌中被甲基化。应该进一步探讨该基因沉默对管腔癌而不是基底样癌的致癌作用的可能性。 PTGS1 诱导前列腺素 E2 (PGE2) 产生，进而刺激芳香酶表达，从而增加局部雌二醇的产生。这是第一份研究人类正常乳腺组织中此类关联的报告。
High serum levels of estradiol are associated with increased risk of postmenopausal breast cancer. Little is known about the gene expression in normal breast tissue in relation to levels of circulating serum estradiol. We compared whole genome expression data of breast tissue samples with serum hormone levels using data from 79 healthy women and 64 breast cancer patients. Significance analysis of microarrays (SAM) was used to identify differentially expressed genes and multivariate linear regression was used to identify independent associations. Six genes (SCGB3A1, RSPO1, TLN2, SLITRK4, DCLK1, PTGS1) were found differentially expressed according to serum estradiol levels (FDR = 0). Three of these independently predicted estradiol levels in a multivariate model, as SCGB3A1 (HIN1) and TLN2 were up-regulated and PTGS1 (COX1) was down-regulated in breast samples from women with high serum estradiol. Serum estradiol, but none of the differentially expressed genes were significantly associated with mammographic density, another strong breast cancer risk factor. In breast carcinomas, expression of GREB1 and AREG was associated with serum estradiol in all cancers and in the subgroup of estrogen receptor positive cases. We have identified genes associated with serum estradiol levels in normal breast tissue and in breast carcinomas. SCGB3A1 is a suggested tumor suppressor gene that inhibits cell growth and invasion and is methylated and down-regulated in many epithelial cancers. Our findings indicate this gene as an important inhibitor of breast cell proliferation in healthy women with high estradiol levels. In the breast, this gene is expressed in luminal cells only and is methylated in non-BRCA-related breast cancers. The possibility of a carcinogenic contribution of silencing of this gene for luminal, but not basal-like cancers should be further explored. PTGS1 induces prostaglandin E2 (PGE2) production which in turn stimulates aromatase expression and hence increases the local production of estradiol. This is the first report studying such associations in normal breast tissue in humans.
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影响因子：
3.5
作者：
Burger, Henry
通讯作者：
Burger, Henry
DOI：
10.1111/j.1742-4658.2009.06893.x
发表时间：
2009-03
期刊：
The FEBS journal
影响因子：
--
作者：
Debrand E;El Jai Y;Spence L;Bate N;Praekelt U;Pritchard CA;Monkley SJ;Critchley DR
通讯作者：
Critchley DR
影响因子：
8.8
作者：
通讯作者：
--
DOI：
10.1093/jnci/90.6.455
发表时间：
1998-03-18
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Hwang, D;Scollard, D;Levine, E
通讯作者：
Levine, E
DOI：
10.1073/pnas.94.20.10937
发表时间：
1997-09-30
影响因子：
11.1
作者：
Cavalieri, EL;Stack, DE;Rogan, EG
通讯作者：
Rogan, EG