Walmer D K, Padin C J, Wrona M A, Healy B E, Bentley R C, Tsao M S, Kohler M F, McLachlan J A, Gray K D
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710.
Cancer Res. 1995 Mar 1;55(5):1168-75.
In the mouse uterus, lactoferrin is a major estrogen-inducible uterine secretory protein, and its expression correlates directly with the period of peak epithelial cell proliferation. In this study, we examine the expression of lactoferrin mRNA and protein in human endometrium, endometrial hyperplasias, and adenocarcinomas using immunohistochemistry, Western immunoblotting, and Northern and in situ RNA hybridization techniques. Our results reveal that lactoferrin is expressed in normal cycling endometrium by a restricted number of glandular epithelial cells located deep in the zona basalis. Two thirds (8 of 12) of the endometrial adenocarcinomas examined overexpress lactoferrin. This tumor-associated increase in lactoferrin expression includes an elevation in the mRNA and protein of individual cells and an increase in the number of cells expressing the protein. In comparison, only 1 of the 10 endometrial hyperplasia specimens examined demonstrates an increase in lactoferrin. We also observe distinct cytoplasmic and nuclear immunostaining patterns under different fixation conditions in both normal and malignant epithelial cells, similar to those previously reported in the mouse reproductive tract. Serial sections of malignant specimens show a good correlation between the localization of lactoferrin mRNA and protein in individual epithelial cells by in situ RNA hybridization and immunohistochemistry. Although the degree of lactoferrin expression in the adenocarcinomas did not correlate with the tumor stage, grade, or depth of invasion in these 12 patients, there was a striking inverse correlation between the presence of progesterone receptors and lactoferrin in all 8 lactoferrin-positive adenocarcinomas. In summary, lactoferrin is expressed in a region of normal endometrium known as the zona basalis which is not shed with menstruation and is frequently overexpressed by progesterone receptor-negative cells in endometrial adenocarcinomas.
在小鼠子宫中，乳铁蛋白是一种主要的雌激素诱导型子宫分泌蛋白，其表达与上皮细胞增殖高峰期直接相关。在本研究中，我们使用免疫组织化学、Western免疫印迹、Northern和原位RNA杂交技术，检测了乳铁蛋白mRNA和蛋白在人子宫内膜、子宫内膜增生和腺癌中的表达。我们的结果显示，乳铁蛋白在正常周期性子宫内膜中由位于基底层深处的少数腺上皮细胞表达。在检测的12例子宫内膜腺癌中，三分之二（8例）过表达乳铁蛋白。这种与肿瘤相关的乳铁蛋白表达增加包括单个细胞中mRNA和蛋白水平的升高以及表达该蛋白的细胞数量增加。相比之下，在检测的10例子宫内膜增生标本中，只有一例显示乳铁蛋白增加。我们还观察到，在正常和恶性上皮细胞中，不同固定条件下存在明显的细胞质和细胞核免疫染色模式，这与先前在小鼠生殖道中报道的模式相似。恶性标本的连续切片显示，通过原位RNA杂交和免疫组织化学检测，单个上皮细胞中乳铁蛋白mRNA和蛋白的定位之间具有良好的相关性。尽管在这12例患者中，腺癌中乳铁蛋白的表达程度与肿瘤分期、分级或浸润深度无关，但在所有8例乳铁蛋白阳性腺癌中，孕激素受体的存在与乳铁蛋白之间存在显著的负相关。总之，乳铁蛋白在正常子宫内膜的一个称为基底层区域表达，该区域在月经时不会脱落，并且在子宫内膜腺癌中经常由孕激素受体阴性细胞过表达。
