ABSTRACT: Pharmacological and endogenous progestins induce vascular
endothelial growth factor expression in human breast cancer cells
Tumor expansion is dependent on angiogenesis, which
is regulated by peptide growth factors of which
vascular endothelial growth factor (VEGF) is one of
the most selective and potent.
VEGF expression is regulated by
steroid hormones in a number of systems, including T47-D human
breast cancer cells in which VEGF protein levels are elevated
In the present study, we investigated the effect
of progestins on VEGF mRNA levels in human breast cancer cells.
For these experiments, T47-D cells were exposed to progestins,
RNA was prepared for measurement of VEGF transcript levels by
Northern blot analysis and VEGF protein in the cell culture media
was measured by enzyme-linked immunosorbent assay. Basal expression
of VEGF mRNA is low in these cells, and is rapidly induced following
exposure to progestins, reaching a maximum induction of 2- to
5-fold between 3 and 6 hr after hormone addition.
was inhibited by the antiprogestin RU-486 indicating that it
is progesterone receptor (PR) dependent. Transcripts for VEGF165
and VEGF121 were the two major spliced forms of VEGF mRNA that
were detected by reverse transcription-polymerase chain reaction
in basal and progestin-stimulated T47-D cells. Maximum induction
of VEGF mRNA was achieved with 10-8 M progesterone, and induction
was hormone specific, as estrogens, glucocorticoids, and androgens
were without effect.
Actinomycin D completely abolished the induction
of VEGF transcript levels by progestins, suggesting that this
response involves de novo mRNA synthesis, but puromycin did not
inhibit induction, suggesting that this effect does not require
This report demonstrates that progestins stimulate
VEGF mRNA levels and raises the possibility that anti-progestins
may be useful to inhibit proliferation and metastasis in some
human breast cancers by blocking VEGF production.
[05/09/2001; International Journal of Cancer]
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