Lessons from pregnancy and parturition: uterine leiomyomas result from discordant differentiation and dedifferentiation responses in smooth muscle cells.

Leiomyomas, benign smooth muscle tumors of the uterus, are the most common gynecological neoplasm in women. Studies with human tissues and primary cultures have revealed little about the development of leiomyomas, although several genes have been shown to be differentially expressed in leiomyomas compared to matched normal myometrium. We propose that uterine smooth muscle tumor cells mimic a differentiated myometrial cell of pregnancy, and are associated with a hypersensitivity to sex steroid hormones, preventing the cells from responding to normal apoptotic or dedifferentiation signals which would return the cells to a nongravid phenotype. Support of this hypothesis is derived from experimental studies in female Eker rats which develop uterine leiomyoma with many similarities to the human disease. Members of the steroid receptor superfamily as well as the binding partners and co-regulators necessary for transactivation and gene transcription, may be involved in the altered pathway of cellular differentiation and regulation observed in uterine leiomyomas.