The unliganded estrogen receptor (ER) transduces growth factor signals.
In the absence of serum and estrogen, we show that the growth of the prolactin secreting pituitary tumour cell line, GH3 is stimulated by insulin and insulin-like growth factor-1 (IGF-1) and this response is blocked by the steroidal antiestrogens, ICI 164384 and ICI 182780. From conditioned medium (CM) experiments, growth of low density cells (10k/cm2) is increased by the addition of CM from high density cells (100k/cm2) and this growth effect is also blocked by antiestrogen. Transfection studies with a delta MTV-ERE-LUC reporter plasmid show that in the absence of estrogen and serum, both insulin and IGF-1 induce luciferase expression and this is blocked by the pure antiestrogens. No effect of these treatments was apparent when parallel experiments were conducted with a plasmid construct lacking the vitellogenin estrogen response element. From these and other data discussed in this report, we conclude that for GH3 cells, in the absence of estrogen and serum, the ER is transcriptionally activated by intracellular peptide factor pathways and by this means, acts as the key nuclear factor inducing mitogenesis in response to autocrine and exogenously added growth factors.
Newton
C J
CJ
Max-Planck-Institute of Psychiatry, Clinical Institute, Munich, Germany.
Buric
R
R
Trapp
T
T
Brockmeier
S
S
Pagotto
U
U
Stalla
G K
GK
D001483:Base Sequence; D002455:Cell Division; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D004967:Estrogens / Q000502:physiology; D000077267:Fulvestrant; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010911:Pituitary Neoplasms / Q000473:pathology; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D004965:Estrogen Antagonists; D004967:Estrogens; D007328:Insulin; D008024:Ligands; D009838:Oligodeoxyribonucleotides; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D000077267:Fulvestrant; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C051781:ICI 164384