Differential effect of estrogen and progesterone on in vitro growth of uterine leiomyoma cells with chromosome 7 deletions

BACKGROUND: The studies on how sex steroid hormones affect growth of uterine leiomyoma cells with chromosomal abnormalities is highly relevant for development of personalized tumor therapy.

AIM: To study in vitro the isolated and combined effects of estrogen and progesterone on uterine leiomyoma cells with chromosomal aberrations — deletions in 7q.

MATERIALS AND METHODS: The study was performed on 15 uterine leiomyomas, excised from 15 women of 26–44 years of age who were not treated with hormones. Uterine leiomyoma cells were cultured in hormone-free medium, in the medium supplemented with estrogen, progesterone or both hormones. The chromosome preparations were made and stained with QFH/AcD to perform conventional karyotyping and fluorescence in situ hybridization (FISH) to accurately describe chromosomal rearrangements. The frequency of uterine leiomyoma cells with chromosomal aberrations was assessed by interphase FISH.

RESULTS: Deletions in 7q were identified in 6 out of 15 karyotyped uterine leiomyomas; four of them had one clone with deletion in 7q whereas two others comprised two clones with 7q deletions of different length. The frequency of cells carrying deletions in 7q greatly varied in uterine leiomyoma samples cultured in hormone-free medium: from 3.5% to 93.6%. Exposure of cell cultures to estrogen and progesterone resulted in a fold change frequency increase in some of the uterine leiomyomas and decrease in the others. The most significant changes in the frequency of cells with deletions in 7q were registered in response to the isolated estrogen and, to a lesser extent, to progesterone exposure; less significant changes were observed after combined hormonal effect.

CONCLUSIONS: In uterine leiomyomas with deletions in 7q, the frequency of abnormal cells may either increase or decrease in response to estrogen and progesterone in vitro supplementation. The isolated effect of estrogen or progesterone on the frequency of uterine leiomyoma cells with deletion in 7q is more pronounced compared to the combined one.