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- Dietary estrogens stimulate human breast cells to enter
the cell cycle.
- Dees C, Foster JS, Ahamed S, Wimalasena J. Environ Health
Perspect 1997 Apr 105 Suppl 3 633-6
- Abstract
- It has been suggested that dietary estrogens neutralize the
effect of synthetic chemicals that mimic the effects of estrogen
(i.e., xenoestrogens, environmental estrogens). Genistein, a dietary
estrogen, inhibits the growth of breast cancer cells at high doses
but additional studies have suggested that at low doses, genistein
stimulates proliferation of breast cancer cells. Therefore, if
dietary estrogens are estrogenic at low doses, one would predict
that they stimulate estrogen-receptor positive breast cancer cells
to enter the cell cycle. Genistein and the fungal toxin zearalenone
were found to increase the activity of cyclin dependent kinase
2 (Cdk2) and cyclin D1 synthesis and stimulate the hyperphosphorylation
of the retinoblastoma susceptibility gene product pRb105 in MCF-7
cells. The steroidal antiestrogen ICI 182,780 suppressed dietary
estrogen-mediated activation of Cdk2. Dietary estrogens not only
failed to suppress DDT-induced Cdk2 activity, but were found to
slightly increase enzyme activity. Both zearalenone and genistein
were found to stimulate the expression of a luciferase reporter
gene under the control of an estrogen response element in MVLN
cells. Our findings are consistent with a conclusion that dietary
estrogens at low concentrations do not act as antiestrogens, but
act like DDT and estradiol to stimulate human breast cancer cells
to enter the cell cycle.
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- Xenoestrogens significantly enhance risk for
breast cancer during growth and adolescence.
- Ardies CM and Dees C. Med Hypotheses 1998 Jun 50:6 457-64
- Abstract
- Breast cancer is one of the most common forms of cancer observed
in women, and endogenous estrogen is thought to play a major role
in its development. Because of this, any conditions or exposures
which enhance estrogenic responses would result in an increased
risk for breast cancer. The role of xenoestrogenic compounds,
such as DDT, in the etiology of breast cancer is still very controversial.
In the following paper we discuss recently-published observations
by ourselves and others which indicate that xenoestrogens may
play a significant role in the development of breast cancer. Specifically,
we hypothesize that during periods of high growth rates and during
breast development the sensitivity of breast cells to estrogenic
compounds is sufficiently great for xenoestrogens to significantly
enhance risk for breast cancer.
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- Author Address
- Health Sciences Research Division, Oak Ridge National Laboratory,
Tennessee, USA.
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