Couse J F, Davis V L, Hanson R B, Jefferson W N, McLachlan J A, Bullock B C, Newbold R R, Korach K S
Laboratory of Reproductive and Developmental Toxicology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, North Carolina 27709, USA.
Mol Carcinog. 1997 Aug;19(4):236-42. doi: 10.1002/(sici)1098-2744(199708)19:4<236::aid-mc4>3.0.co;2-a.
The role of estrogen and the estrogen receptor (ER) in the induction and promotion of tumors was investigated by using transgenic MT-mER mice, which overexpress the ER. It was hypothesized that because of this abnormal expression of the ER, the reproductive-tract tissues of the MT-mER mice may be more susceptible to tumors after neonatal exposure to the potent synthetic estrogen diethylstilbestrol (DES). Normally non-estrogen responsive tissues that may have expressed ER as a result of the transgene were also studied for DES-induced tumors. Wild-type and MT-mER littermates were treated with 2 micrograms/pup/d DES 1-5 d after birth and then killed at 4, 8, 12, and 18 mo of age. The DES-treated MT-mER mice demonstrated a significantly higher incidence of uterine adenocarcinoma at 8 mo (73%) than the DES-treated wild-type mice (46%). The tumors of the MT-mER mice were often more aggressive than those in the wild-type animals. These tumors were also preceeded at 4 mo by a significantly higher incidence of the preneoplastic lesion atypical hyperplasia in the MT-mER mice (26% compared with 0% in the wild-type mice). Other DES-induced abnormalities were observed at equal rates in the wild-type and MT-mER mice. Although no tumors were observed in untreated wild-type females, a single untreated MT-mER female had uterine adenocarcinoma at 18 mo. These data indicate that the level of ER present in a tissue may also be a determining factor in development of estrogen-responsive tumors.
通过使用过表达雌激素受体（ER）的转基因MT - mER小鼠，研究了雌激素和雌激素受体（ER）在肿瘤诱导和促进中的作用。据推测，由于ER的这种异常表达，MT - mER小鼠的生殖道组织在新生期暴露于强效合成雌激素己烯雌酚（DES）后可能更容易发生肿瘤。还研究了可能因转基因而表达ER的正常非雌激素反应性组织中的DES诱导肿瘤。野生型和MT - mER同窝小鼠在出生后1 - 5天用2微克/幼崽/天的DES处理，然后在4、8、12和18月龄时处死。经DES处理的MT - mER小鼠在8月龄时子宫腺癌的发生率（73%）显著高于经DES处理的野生型小鼠（46%）。MT - mER小鼠的肿瘤通常比野生型动物的肿瘤更具侵袭性。在4月龄时，MT - mER小鼠的癌前病变非典型增生的发生率也显著更高（26%，而野生型小鼠为0%），随后出现这些肿瘤。在野生型和MT - mER小鼠中观察到的其他DES诱导的异常情况发生率相同。虽然在未处理的野生型雌性小鼠中未观察到肿瘤，但有一只未处理的MT - mER雌性小鼠在18月龄时患有子宫腺癌。这些数据表明，组织中存在的ER水平也可能是雌激素反应性肿瘤发生发展的一个决定因素。
