Perel E, Blackstein M E, Killinger D W
Cancer Res. 1982 Aug;42(8 Suppl):3369s-3372s.
Breast carcinoma tissue is capable of forming estrogens from circulating androgen precursors. In this study, aromatase was examined in homogenates of breast adipose and breast carcinoma tissue, in normal and abnormal parenchymal breast tissue, and in breast carcinoma cells in culture. Homogenates of carcinoma tissue showed a wide range of activity in the conversion of adrostenedione to estrone. The mean conversion in carcinoma tissue was greater than that seen in parenchymal tissue from patients with gynecomastia and mammary dysplasia. Homogenates of breast adipose tissue from patients with benign and malignant disorders showed comparable aromatase activity. Three cell lines isolated from a primary breast carcinoma differed in their aromatase activity demonstrating a heterogeneity of aromatase activity in cells from a single tumor. Studies of aromatase activity in breast carcinoma cells in culture over a period of 8 hr demonstrated progressive estrone formation. Testosterone formation from androstenedione was noted in all studies using both homogenates and cell cultures. Testosterone formation from androstenedione was approximately 10-fold greater than was the formation of estrone from androstenedione in all studies. The metabolism of androstenedione to other androgens examined in homogenates of normal and carcinomatous breast tissue revealed that the major products were androsterone, 5 beta-androsterone, dihydrotestosterone, and epiandrosterone. Both estrogen and androgen formation within the cell may be important in determining the cellular response.
乳腺癌组织能够从循环的雄激素前体生成雌激素。在本研究中，对乳腺脂肪组织和乳腺癌组织的匀浆、正常和异常的乳腺实质组织以及培养的乳腺癌细胞中的芳香化酶进行了检测。癌组织匀浆在将雄烯二酮转化为雌酮的过程中表现出广泛的活性范围。癌组织中的平均转化率高于男性乳房发育症和乳腺发育异常患者实质组织中的转化率。患有良性和恶性疾病患者的乳腺脂肪组织匀浆显示出相当的芳香化酶活性。从原发性乳腺癌分离出的三种细胞系在芳香化酶活性方面存在差异，表明单个肿瘤细胞中芳香化酶活性具有异质性。对培养8小时的乳腺癌细胞中的芳香化酶活性研究表明，雌酮的生成呈渐进性。在使用匀浆和细胞培养的所有研究中，均观察到从雄烯二酮生成睾酮的现象。在所有研究中，从雄烯二酮生成睾酮的量大约是从雄烯二酮生成雌酮量的10倍。在正常和癌性乳腺组织匀浆中检测到的雄烯二酮向其他雄激素的代谢表明，主要产物是雄酮、5β - 雄酮、双氢睾酮和表雄酮。细胞内雌激素和雄激素的生成在决定细胞反应方面可能都很重要。
