Although
steroid hormones are known to play a predominant role in the regulation of cell growth in
hormone-sensitive
cancers, their mechanisms of action, especially their interaction with
growth factors and/or
growth inhibitors, is poorly understood. We have recently observed that the effects of
androgens and
estrogens on the expression of the major
protein found in human breast gross cystic disease fluid, protein-24, are opposite to their respective action on cell proliferation in human
breast cancer cell lines. Somewhat surprisingly, the recent elucidation of the amino acid sequence of this
progesterone binding protein reveals that this
tumor marker is
apolipoprotein D (
apo D), a member of a superfamily of lipophilic
ligand carrier proteins. The present study was designed to determine whether
apo D is secreted by human
prostate cancer cells and could thus be a new marker of
steroid action in these
cancer cells, and whether the sex
steroid-induced stimulation of
apo D secretion coincides with inhibition of cell proliferation. We took advantage of the biphasic pattern of the effect of
steroids on the proliferation of the human
prostate cancer LNCaP cell line, which offers the opportunity to discriminate between positive and negative
steroid receptor-regulated cell growth processes. A 10-day exposure to low concentrations of
dihydrotestosterone and
testosterone caused a potent stimulation of LNCaP cell proliferation, whereas incubation with higher concentrations of these
androgens led to a progressive decrease in cell proliferation towards basal levels. The biphasic action of
androgens was also observed on
apo D secretion, the effects on
apo D secretion being inversely related to their action on LNCaP cell proliferation. Similar opposite biphasic effects were also observed with 9 other
steroids, thus indicating that the stimulation of secretion of this new
biochemical marker coincides with inhibition of cell proliferation in LNCaP human
prostatic cancer cells.