Ch. Chien et al., TRANSCRIPTIONAL ACTIVATION OF C-MYC PROTOONCOGENE BY ESTROGEN IN HUMAN OVARIAN-CANCER CELLS, Molecular and cellular endocrinology, 99(1), 1994, pp. 11-19
NIH:OVCAR-3 is a human ovarian cancer cell line that expresses a moder
ate amount of estrogen receptors, 28 fmol/mg protein. We have found th
at estrogen at a concentration of 10(-7) M induced a 2.3-fold increase
in the growth of NIH:OVCAR-3 cells after 48 h stimulation. A 4-fold i
ncrease in c-myc mRNA expression at 30 min and a 7.5-fold increase at
50 min post-induction with estradiol were observed. Nuclear run-on ana
lysis indicated that c-myc transcripts increased 4-fold within 10 min
of estrogen addition. The half-life of c-myc mRNA was 64 min +/- 5 min
and was not affected by estrogen. Antisense oligonucleotide to c-myc
specifically inhibited the estrogen stimulated c-myc protein expressio
n as well as the growth of NIH:OVCAR-3 cells. A control ovarian cancer
cell line OC-3-VGH that had few estrogen receptors (1 fmol/mg protein
) did not respond to estrogen in growth; however, these cells respond
to estrogen with a 1.5-fold increase in c-myc mRNA. The stability of c
-myc mRNA of these cells was not affected by estrogen. Our results ind
icate that transcriptional induction of c-myc expression by estrogen p
lays a critical role in the proliferation of NIH:OVCAR-3 cells.