Biological impact of a disrupted estrogen receptor gene on estrogen-related cancer

The development of the ERKO mouse has demonstrated that the estrogen receptor is not required for survival. Subsequently, the first case of estrogen insensitivity in a human male, caused by a naturally occurring mutation of the estrogen receptor gene, was reported (Smith et al. 1994). The lack of a functional estrogen receptor in the mouse clearly had an impact on the growth and development of tissues normally considered to be estrogen- responsive (i.e. mammary gland, uterus, ovary). Estrogen/estrogen receptor action has been associated with carcinogenesis in these tissues, therefore the ERKO mouse provides a model to study the role of estrogen receptor in tumor initiation and promotion. In addition, the ERKO mouse model has become invaluable in analyzing the presence and function of ERβ in the development of tissues without comfounding activity from the classical estrogen receptor (Couse et al. 1997b). The analysis of ERβ in estrogen-responsive tissues that are susceptible to carcinogenesis will also be important. Although not covered in this review, the ERKO mouse has also provided insight into the physiological role of estrogen receptor in bone development (Korach et al. 1997b), cardiovascular function (Johns et al. 1996), sexual behavior (Ogawa et al. 1996, 1997) and reproduction (Lubahn et al. 1993, Couse et al. 1995b, Eddy et al. 1996).