DNA content and chromatin texture of human breast epithelial cells transformed with 17-beta-estradiol and the estrogen antagonist ICI 182,780 as assessed by image analysis.
The immortalized human breast epithelial MCF-10F cell line, although estrogen receptor alpha negative, develops cell proliferating activities and invasiveness indicative of neoplastic transformation, after treatment with 17-beta-estradiol (E-2). These effects are similar to those produced by benzo[a]pyrene (BP). Since we have previously reported changes in the nuclear parameters accompanying BP-induced tumorigenesis in MCF-10F cells, we have examined whether similar alterations occur in E-2-treated cells. We therefore studied DNA amounts and other nuclear parameters in Feulgen-stained MCF-10F cells after treatment with various concentrations of E-2, BP, the estrogen antagonist ICI 182,780, and E-2 in the presence of ICI 182,780. E-2 caused a certain loss of DNA and changes in the nuclear size and chromatin supraorganization of MCF-10F cells. Many of these changes were similar to those produced by BP and were indicative of neoplastic transformation. More intense chromatin remodelling was seen with 70 nM E-2. Since these changes were not abrogated totally or partially by ICI 182,780, the neoplastic transformation of MCF-10F cells stimulated by E-2 involved a process that was independent of estrogen alpha-receptors. The changes produced by ICI 182,780 alone were attributed to effects other than its well-known anti-estrogenic activity.
Mello
Maria Luiza S
ML
Department of Cell Biology, Institute of Biology, UNICAMP, 13083-863 Campinas, SP, Brazil. mlsmello@unicamp.br
Vidal
Benedicto C
BC
Russo
Irma H
IH
Lareef
Mohamed H
MH
Russo
Jose
J
D001564:Benzo(a)pyrene / Q000494:pharmacology; D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000235:genetics*; D002461:Cell Line, Transformed; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics; D002843:Chromatin / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis*; D004847:Epithelial Cells / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D019044:Image Cytometry
D002843:Chromatin; D004273:DNA, Neoplasm; D004965:Estrogen Antagonists; D000077267:Fulvestrant; D001564:Benzo(a)pyrene; D004958:Estradiol