Lessons from pregnancy and parturition: uterine leiomyomas result front 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 cul tures have revealed little about the development of leiomyomas, although se veral genes have been shown to be differentially expressed in leiomyomas co mpared to matched normal myometrium. We propose that uterine smooth muscle tumor cells mimic a differentiated myometrial cell of pregnancy, and are as sociated with a hypersensitivity to sex steroid hormones, preventing the ce lls 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 ute rine leiomyoma with many similarities to the human disease. Members of the steroid receptor superfamily as well as the binding partners and cc-regulat ors necessary for transactivation and gene transcription, may be involved i n the altered pathway of cellular differentiation and regulation observed i n uterine leiomyomas. (C) 2000 Harcourt Publishers Ltd.