Gene Expression Patterns in the Human Breast after Pregnancy
Gene Expression Patterns in the Human Breast after Pregnancy
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DOI：
10.1158/1940-6207.capr-09-0069
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发表时间：
2010-03-01
影响因子：
3.3
通讯作者：
Tonetti, Debra A.
中科院分区：
文献类型：
--
作者：
Asztalos, Szilard;Gann, Peter H.;Tonetti, Debra A.
流行病学研究表明，怀孕对乳腺癌风险具有双向的、时间依赖性的影响;风险升高期之后是长期的保护期。本研究的目的是确定妊娠和退化是否与正常乳腺的基因表达变化有关，以及这种变化是短暂的还是持续的。我们检查了未经生育、最近怀孕（怀孕0-2年）和远距离怀孕（怀孕5-10年）年龄匹配的绝经前女性的正常乳腺组织中定制基因集的表达。该基因集包括乳腺癌生物标志物和与免疫/炎症、细胞外基质重塑、血管生成和激素信号传导相关的基因。激光捕获显微切割和RNA提取从福尔马林固定的石蜡包埋的乳房缩小术和良性活检标本，并使用实时PCR阵列包含59个路径特异性和5管家基因进行分析。我们报告了64个基因中的14个（22%）在未经产乳腺组织与经产乳腺组织中差异调节（P < 0.05）。基于基因集分析，炎症相关基因作为一个组在两个经产组与未经产妇女相比，显着上调（P = 0.03）。此外，与未经产受试者相比，经产受试者的雌激素受体α（ER α，ESR 1）、孕激素受体（PGR）和ERBB 2（Her 2/neu）表达显著降低，雌激素受体β（ESR 2）表达高2倍。这些最初的数据是关于正常人类乳腺样本中基因表达的第一批数据，为怀孕对乳腺癌风险的时间依赖性影响背后的机制提供了有趣的线索。Cancer Prev Res; 3（3）; 301-11. (C)2010年AACR。
Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal breast, and whether such changes are transient or persistent. We examined the expression of a customized gene set in normal breast tissue from nulliparous, recently pregnant (0-2 years since pregnancy), and distantly pregnant (5-10 years since pregnancy) age-matched premenopausal women. This gene set included breast cancer biomarkers and genes related to immune/inflammation, extracellular matrix remodeling, angiogenesis, and hormone signaling. Laser capture microdissection and RNA extraction were done from formalin-fixed paraffin-embedded reduction mammoplasty and benign biopsy specimens and analyzed using real-time PCR arrays containing 59 pathway-specific and 5 housekeeping genes. We report 14 of 64 (22%) of the selected gene set to be differentially regulated (at P < 0.05 level) in nulliparous versus parous breast tissues. Based on gene set analysis, inflammation-associated genes were significantly upregulated as a group in both parous groups compared with nulliparous women (P = 0.03). Moreover, parous subjects had significantly reduced expression of estrogen receptor alpha (ER alpha, ESR1), progesterone receptor (PGR), and ERBB2 (Her2/neu) and 2-fold higher estrogen receptor-beta (ESR2) expression compared with nulliparous subjects. These initial data, among the first on gene expression in samples of normal human breast, provide intriguing clues about the mechanisms behind the time-dependent effects of pregnancy on breast cancer risk. Cancer Prev Res; 3(3); 301-11. (C) 2010 AACR.