Oestrogen directly stimulates growth factor signal transduction pathways in human breast cancer cells.
We have studied the mechanism by which 17 beta-oestradiol (E2) stimulates breast cancer proliferation using the MCF7 cell line as a model system. We provide evidence that E2 directly stimulates cellular proliferation by inducing, like many growth factors, the c-fos proto-oncogene. E2 by itself, however, is poorly mitogenic and it does not induce genes from the jun family, whose gene products are necessary for heterodimerization with the c-fos encoded protein (Fos), leading to an important step in growth factor signalling pathways, stimulation of the 12-O-tetradecanoyl-phorbol-13-acetate responsive element (TRE)-dependent transcriptional activity. In combination with insulin-like growth factors (IGFs), efficient inducers of c-jun in breast cancer cells, E2 synergistically stimulates TRE-activity and proliferation. This direct stimulation by E2 of growth factor signalling pathways suggest that E2 can directly induce proliferation, independent from autocrine growth factors.
van der Burg
B
B
Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
de Groot
R P
RP
Isbrücker
L
L
Kruijer
W
W
de Laat
S W
SW
D015152:Blotting, Northern; D001943:Breast Neoplasms / Q000378:metabolism*; D015500:Chloramphenicol O-Acetyltransferase / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004967:Estrogens / Q000502:physiology*; D005260:Female; D006801:Humans; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D004967:Estrogens; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D012334:RNA, Neoplasm; D015500:Chloramphenicol O-Acetyltransferase; D013755:Tetradecanoylphorbol Acetate