Estradiol stimulates c-myc proto-oncogene expression in normal human breast epithelial cells in culture.
The proto-oncogene c-myc is involved in the stimulation of cell proliferation, and its expression is known to be stimulated by estradiol (E2) in human breast cancer cell lines and various non-cancerous E2-dependent tissues. However, little information is currently available concerning its expression and regulation in normal human breast tissue. We therefore studied c-myc expression and hormone modulation in normal human breast epithelial (HBE) cells in culture, routinely obtained in our laboratory and which remain hormone-dependent. On these normal HBE cells, E2 induced a biphasic increase in c-myc mRNA level, with a first peak as early as 30 min, and a secondary increase after 2 h of treatment; this stimulation was dose-dependent, with an optimal concentration of 10 nM E2. Its primary action is probably at the transcriptional level since the half-life of c-myc mRNA measured in the presence of actinomycin D (12 +/- 3 min) was not modified by E2 treatment. In addition, E2 stimulation of c-myc mRNA does not require protein synthesis since it was not suppressed by cycloheximide treatment. Western blot studies of c-myc protein in HBE cells revealed the same biphasic pattern of stimulation, with a first peak after 60 min and a second one after 2 h of E2 treatment. In conclusion, the c-myc proto-oncogene is expressed in normal HBE cells, as in breast cancer cells. Moreover, E2 stimulates c-myc expression which, therefore, may partly mediate the growth-promoting effect of E2.
Leygue
E
E
Department of Reproductive Medicine, Hôpital Necker, Paris, France.
Gol-Winkler
R
R
Gompel
A
A
Louis-Sylvestre
C
C
Soquet
L
L
Staub
S
S
Kuttenn
F
F
Mauvais-Jarvis
P
P
D001940:Breast / Q000166:cytology / Q000187:drug effects*; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells; D004848:Epithelium / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D003609:Dactinomycin; D004958:Estradiol; D003513:Cycloheximide