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

Abstract

Background: The studies on how sex steroid hormones affect growth of uterine leiomyoma (UL) 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 UL cells with chromosomal aberrations deletions in 7q. Materials and Methods: The study was performed on 15 ULs, excised from 15 women of 26-44 years of age who were not treated with hormones. UL 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 UL cells with chromosomal aberrations was assessed by interphase FISH. Results: Deletions in 7q were identified in 6 out of 15 karyotyped ULs; 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 UL 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 ULs 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 ULs 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 UL cells with deletion in 7q is more pronounced compared to the combined one.