Tumour necrosis factor-alpha modulates oestradiol responsiveness of MCF-7 breast cancer cells in vitro.
We studied the effect of tumour necrosis factor-alpha (TNF) on oestradiol regulation of growth and metabolism of MCF-7 breast cancer cells to determine whether TNF altered the oestradiol responsiveness of these cells. We found that TNF antagonized oestradiol stimulation of cell growth in a dose-dependent manner, with partial inhibition at 1.0 U/ml and complete inhibition at 1000 U/ml. TNF inhibited cell cycle progression, increasing cells in the G0G1 phase and blocking oestradiol-stimulated progression into the S phase. We examined the effect of TNF on three oestrogen-regulated proteins, the oestrogen receptor (ER), the progesterone receptor (PR) and insulin-like growth factor-I (IGF-I). TNF down-regulated the ER and up-regulated the PR. Both of these processes were enhanced by the addition of oestradiol. The effects of TNF on the ER and PR were dose-dependent and occurred without a change in the Kd of the receptor. TNF did not change the respective steady-state mRNA levels. In addition, TNF did not alter secretion of IGF-I either in the absence or presence of oestradiol, indicating that the effects of TNF on oestrogen-regulated proteins in selective. These findings indicate an important interaction between the immune and endocrine systems. The cytokine TNF has a prominent effect on oestradiol stimulation of MCF-7 cells, blocking its proliferative response and enhancing certain metabolic effects. These actions may be mediated in part through modulation of the ER, although other pathways appear to be involved.
Danforth
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Surgery Branch, National Cancer Institute, Bethesda, Maryland 20892.
Sgagias
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D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000187:drug effects; D007700:Kinetics; D011960:Receptors, Estrogen / Q000187:drug effects; D011980:Receptors, Progesterone / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D004965:Estrogen Antagonists; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014409:Tumor Necrosis Factor-alpha; D004958:Estradiol; D007334:Insulin-Like Growth Factor I