The oestrogen receptor modulates growth of pituitary tumour cells in the absence of exogenous oestrogen.
The GH3 pituitary cell line has been used to investigate the role of the oestrogen receptor (ER) as a modulator of mitogenic signals in tumour cells in the absence of exogenous oestrogen. Using a chemically defined, serum- and oestrogen-free medium, we have demonstrated that the pure steroidal anti-oestrogens ICI 182780 and ICI 164384 are capable of blocking growth by more than 50% after 5 days of culture. Studies with conditioned medium have indicated that the basal growth is due to the secretion of autocrine growth stimulatory substances. Under serum- and oestrogen-free conditions, insulin and IGF-I increased the growth rate of these cells by twofold over a 5-day treatment period, and this effect was also blocked by the anti-oestrogens ICI 182780 and ICI 164384 (50% of maximum inhibition at 0.6 and 6 nM respectively). To explore the potential mechanism by which the ER apparently facilitates the growth factor effects under oestrogen-free conditions, GH3 cells were transiently transfected with a plasmid reporter containing the vitellogenin oestrogen response element (delta MTV-ERE-LUC). We have shown that as well as oestradiol (OE2), insulin and IGF-I induce luciferase activity by between two- and sevenfold (four experiments), and these effects were completely blocked by ICI 182780. In contrast, growth factors and OE2 were unable to induce luciferase expression when transfections were performed with a plasmid reporter lacking the oestrogen response element. The studies presented here strongly suggest that, in the absence of oestrogen, the ER in these pituitary tumour cells has a role in growth, as peptide factors are able to induce its conversion to a state which is capable of up-regulating the transcription of key growth-promoting genes.
Newton
C J
CJ
Max-Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
Trapp
T
T
Pagotto
U
U
Renner
U
U
Buric
R
R
Stalla
G K
GK
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D000077267:Fulvestrant; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000187:drug effects / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000473:pathology*; D053284:Polyunsaturated Alkamides; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014819:Vitellogenins / Q000235:genetics
D016895:Culture Media, Serum-Free; D007328:Insulin; D009363:Neoplasm Proteins; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D014819:Vitellogenins; D000077267:Fulvestrant; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C051781:ICI 164384