Shidfar Ali, Fatokun Tolulope, Ivancic David, Chatterton Robert T, Khan Seema A, Wang Jun
Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Department of Obstetrics & Gynecology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Horm Cancer. 2016 Aug;7(4):252-9. doi: 10.1007/s12672-016-0264-3. Epub 2016 Apr 19.
The local endocrine environment of the breast may have stronger relations to breast cancer risk than systemic hormones. Nipple aspiration fluid (NAF) provides a window into this milieu. We hypothesized that the correlations between proteins and steroid hormones in NAF are stronger, and specific relationships may reveal links to breast cancer risk. NAF and blood samples were obtained simultaneously from 54 healthy women and from the contralateral unaffected breast of 60 breast cancer patients. The abundance of five proteins, superoxide dismutase (SOD1), C-reactive protein (CRP), chitinase-3-like protein 1 (YKL40), cathepsin D (CatD), and basic fibroblast growth factor (bFGF) in NAF was measured using ELISA. The NAF and serum concentrations of estradiol, estrone, progesterone, androstenedione, testosterone, and dehydroepiandrostrerone (DHEA) were measured using ELISA or RIA. The correlations between proteins and hormones revealed that NAF proteins correlated with each other: SOD1 with CRP (R = 0.276, P = 0.033) and CatD (R = 0.340, P = 0.0036), and bFGF with CRP (R = 0.343, P = 0.0021). NAF proteins displayed significant correlations with NAF steroids, but not with serum steroids: SOD1 with DHEA (R = 0.333, P = 0.019), YKL40 with testosterone (R = 0.389, P = 0.0012), and bFGF negatively correlated with testosterone (R = -0.339, P = 0.015). The regulation of YKL40 and bFGF by testosterone was confirmed in breast cancer cell lines. In summary, NAF proteins were more strongly related to local hormone levels than to systematic hormone levels. Some proteins were specifically correlated with different NAF steroids, suggesting that these steroids may contribute to breast cancer risk through different mechanisms.
乳腺的局部内分泌环境与乳腺癌风险的关系可能比全身激素更为密切。乳头抽吸液（NAF）为了解这一环境提供了一个窗口。我们推测，NAF中蛋白质与类固醇激素之间的相关性更强，特定的关系可能揭示与乳腺癌风险的联系。同时从54名健康女性以及60名乳腺癌患者对侧未受影响的乳房中采集NAF和血液样本。使用酶联免疫吸附测定（ELISA）法检测NAF中五种蛋白质，即超氧化物歧化酶（SOD1）、C反应蛋白（CRP）、几丁质酶3样蛋白1（YKL40）、组织蛋白酶D（CatD）和碱性成纤维细胞生长因子（bFGF）的丰度。使用ELISA或放射免疫分析（RIA）法检测NAF和血清中雌二醇、雌酮、孕酮、雄烯二酮、睾酮和脱氢表雄酮（DHEA）的浓度。蛋白质与激素之间的相关性显示，NAF中的蛋白质相互关联：SOD1与CRP（R = 0.276，P = 0.033）以及CatD（R = 0.340，P = 0.0036）相关，bFGF与CRP（R = 0.343，P = 0.0021）相关。NAF中的蛋白质与NAF中的类固醇有显著相关性，但与血清类固醇无相关性：SOD1与DHEA（R = 0.333，P = 0.019）相关，YKL40与睾酮（R = 0.389，P = 0.0012）相关，bFGF与睾酮呈负相关（R = -0.339，P = 0.015）。在乳腺癌细胞系中证实了睾酮对YKL40和bFGF的调节作用。总之，NAF中的蛋白质与局部激素水平的关系比与全身激素水平的关系更为密切。一些蛋白质与不同的NAF类固醇有特定相关性，表明这些类固醇可能通过不同机制影响乳腺癌风险。
