Joyeux C, Chalbos D, Rochefort H
Institut National de la Santé et de la Recherche Medicale, Unité Hormones et Cancer, Montpellier, France.
J Clin Endocrinol Metab. 1990 May;70(5):1438-44. doi: 10.1210/jcem-70-5-1438.
Fatty acid synthetase (FAS) is induced by progestins in human breast cancer cell lines. To study its regulation in normal mammary glands, the FAS level was estimated by immunohistochemistry, using the biotin-streptavidin method, in ducts and lobules of normal tissues adjacent to nonproliferative benign breast lesions collected by biopsy. Rabbit polyclonal antibodies to human FAS specifically recognized the 250-kDa FAS from MCF7 cells, as shown by Western immunoblotting. An excess of purified FAS totally switched off FAS immunostaining of R5020-treated MCF7 cells, demonstrating the validity of FAS immunocytochemical detection. FAS labeling was quantified using a computer-aided image analyzer (SAMBA 2005) in 18 patients receiving progestin therapy from the 15th to the 25th day of the menstrual cycle and 26 untreated patients. In the 2 groups, FAS staining, absent of fibroblasts, was observed in the cytoplasm of epithelial cells. It was higher in lobules than in ducts and increased significantly from the follicular to the luteal phase in both structures. Progestin treatment increased FAS expression in both structures. Using monoclonal antibodies, progesterone receptor expression was measured in frozen serial sections. In patients receiving progestin treatment, the progesterone receptor level increased from the beginning of the cycle to day 14 and then decreased during the second part of the menstrual cycle, probably down-regulated by progestin, indicating a regulation similar to that in the endometrium. We conclude that FAS is induced by progestins in the ducts and lobules of human normal mammary glands as it is in human breast cancer cells. FAS may, therefore, be useful for studying the effect of progesterone in normal human mammary glands.
脂肪酸合成酶（FAS）在人乳腺癌细胞系中由孕激素诱导产生。为了研究其在正常乳腺中的调节机制，采用生物素-链霉亲和素法，通过免疫组织化学对活检收集的非增殖性良性乳腺病变旁正常组织的导管和小叶中的FAS水平进行了评估。如Western免疫印迹所示，兔抗人FAS多克隆抗体能特异性识别MCF7细胞中的250-kDa FAS。过量的纯化FAS完全阻断了R5020处理的MCF7细胞的FAS免疫染色，证明了FAS免疫细胞化学检测的有效性。使用计算机辅助图像分析仪（SAMBA 2005）对18例在月经周期第15至25天接受孕激素治疗的患者和26例未治疗患者的FAS标记进行了定量分析。在两组中，在成纤维细胞不存在的情况下，上皮细胞的细胞质中观察到FAS染色。小叶中的FAS染色高于导管，并且在两个结构中从卵泡期到黄体期均显著增加。孕激素治疗增加了两个结构中的FAS表达。使用单克隆抗体，在冷冻连续切片中测量孕激素受体表达。在接受孕激素治疗的患者中，孕激素受体水平从周期开始到第14天升高，然后在月经周期的第二部分下降，可能是由孕激素下调，表明其调节与子宫内膜相似。我们得出结论，FAS在人正常乳腺的导管和小叶中由孕激素诱导产生，就像在人乳腺癌细胞中一样。因此，FAS可能有助于研究孕激素在人正常乳腺中的作用。
