Accelerated onset of uterine tumors in transgenic mice with aberrant expression of the estrogen receptor after neonatal exposure to diethylstilbestrol

Mol Carcinog. 1997 Aug;19(4):236-42. doi: 10.1002/(sici)1098-2744(199708)19:4<236::aid-mc4>;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.

MeSH terms

  • Adenocarcinoma / chemically induced*
  • Adenocarcinoma / ultrastructure*
  • Animals
  • Body Weight / drug effects
  • Carcinogens / toxicity*
  • Cocarcinogenesis*
  • Diethylstilbestrol / toxicity*
  • Female
  • Hyperplasia / chemically induced
  • Metaplasia / chemically induced
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Receptors, Estrogen / biosynthesis*
  • Receptors, Estrogen / metabolism
  • Uterine Neoplasms / chemically induced*
  • Uterine Neoplasms / ultrastructure*
  • Uterus / drug effects
  • Uterus / metabolism
  • Uterus / pathology


  • Carcinogens
  • Receptors, Estrogen
  • Diethylstilbestrol