title: Interleukin 1 alpha blocks estradiol-stimulated growth and down-regulates the estrogen receptor in MCF-7 breast cancer cells in vitro.
abstract: We studied the effect of interleukin 1 alpha (IL-1 alpha) on estradiol stimulation of cell growth and estrogen receptor (ER) content in MCF-7 human breast cancer cells in vitro to determine if IL-1 alpha altered cellular estradiol responsiveness. We found that IL-1 alpha blocked estradiol-stimulated growth of these cells in a dose-dependent manner (complete antagonism at 1000 units/ml: day 7 mean growth = vehicle, 47.7 micrograms DNA; estradiol 10(-10) M, 95.1; IL-1 alpha/estradiol, 44.6) and at all concentrations of estradiol from 10(-8) to 10(-11) M. IL-1 alpha in combination with trans-hydroxytamoxifen further inhibited estradiol-stimulated growth (vehicle = 44.8 micrograms DNA, estradiol = 108.3, estradiol/trans-hydroxytamoxifen = 47.8, IL-1 alpha/estradiol/trans-hydroxytamoxifen = 3.0, P less than 0.01). Inhibition with trans-hydroxytamoxifen was IL-1 alpha dose dependent (maximum = 97% at 1000 units/ml, P less than 0.01) and estradiol dose dependent (reversible with 10(-8) M estradiol, maximum inhibition at 10(-10) M estradiol). Concomitantly, IL-1 alpha down-regulated ER concentration by 38.0-43.7% (P less than 0.01) as measured by immunoreactivity or Scatchard analysis, respectively. This occurred as early as 3 h without a change in the Kd (vehicle = 0.23 nM, IL-1 alpha = 0.24 nM), persisted for at least 48 h, was dose dependent (maximum, 43.7% at 1000 units/ml, P less than 0.01), and was blocked by cycloheximide. IL-1 alpha, however, did not block estradiol stimulation of progesterone receptor content (vehicle = 221.9, IL-1 alpha = 238.9 fmol/mg protein) and did not block estradiol down-regulation of ER content. Furthermore, IL-1 alpha alone did not alter levels of ER mRNA and did not alter estradiol down-regulation of ER mRNA. These findings indicate that while IL-1 alpha antagonizes estradiol stimulation of growth and reduces ER content, its mechanism may involve other non-estrogen-regulated pathways.
authors.affiliation: Surgery Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
authors.forename: D N
authors.initials: DN
authors.lastname: Danforth
authors.forename: M K
authors.initials: MK
authors.lastname: Sgagias
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis* / Q000235:genetics; D011980:Receptors, Progesterone / Q000032:analysis / Q000235:genetics; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; C038345:droloxifene; D004958:Estradiol