Estrogen-induced proliferation

Simard J, Labrie C, Belanger A, Gauthier S, Singh SM, Merand Y, Labrie F (1997) Characterization of the effects of the novel non-steroidal antiestrogen EM-800 on basal and estrogen-induced proliferation of T-47D, ZR-75-1 and MCF-7 human breast cancer cells in vitro. Int J Cancer 73 104-112... 

Progesterone induces characteristic morphological changes of the endometrium after estrogen-induced proliferation of this tissue. This effect is the basis of the endometrium transformation assay, in which immature rabbits are primed with estradiol for several days and are subsequently treated with a progestin, either by oral application or by subcutaneous injection. The proliferating response of the uterus is examined by histological analysis and quantitated with the McPhail index on a scale from 1 to 4, with 4 as maximal effect. The assay is very sensitive and specific, even if the rabbit expresses only the B isoform of PR. 

Combination oral contraceptives actually cause a 50% decrease in the incidence of endometrial cancer that lasts 15 years after the pills are stopped. This is thought to be due to the inclusion of a progestin, which opposes estrogen-induced proliferation, throughout the entire 21 days. These agents also decrease the incidence of ovarian cancer and may decrease the risk of colorectal cancer. 

Associated with Estrogen-Induced Proliferation of Human Breast Cancer Cells. Cancer... 

Bhalla RC, Toth KF, Bhatty RA, Thompson LP, Sharma RV (1997) Estrogen reduces proliferation and agonist-induced calcium increase in coronary artery smooth muscle cells. Am J Physiol 272 H 1996-2003... 

Later, Fuchs-Young et al. (1996) demonstrated that raloxifene inhibited proliferation of rat leiomyoma cells in culture. In the same year, in one of the first reviews of the pharmacology of raloxifene, Bryant et al. (1996) showed that raloxifene exerted on animal models a dose-related capacity for blocking estrogen-induced stimulation of uterine weight gain. 

Substances such as promoters that interfere with cell-to-cell communication allow cancer cells to proliferate wildly. But cell proliferation can be induced by other means as well. Toxicity or other types of injury to tissues can result in a proliferative response. So can certain natural and synthetic hormones, such as estrogens, cause proliferation of certain tissues, such as the breast. Chronic viral infections may cause cell killing and its consequence is cell proliferation. It appears that sustained chronic proliferation induced in any of these ways, either by agents foreign to the body or some, such as the estrogens, that are natural to it, can increase tumor growth. 

The results described above show that none of the compound tested exerts a more potent antagonistic effect than the novel nonsteroidal compound EM-652 on E2 induced proliferation in T-47D, ZR-75-1, and MCF-7 human breast cancer cells in vitro. Most importantly, EM-652 and EM-800 have no estrogenic activity in the three breast cancer cell lines studied, whereas raloxifene, hydroxytamox-ifen, toremifene, and droloxifene cause a significant stimulation of... 

As described in an earlier section, estrogen induces its physiological action by binding with specific receptors in the plasma membrane and eventually triggering multiple gene activations to carry out cell proliferation and differentiation. It is now established that estrogen receptors themselves cannot carry out the transcription alone, but need an... 

In a hormone-responsive endometrial cell line (ECC-1), a methanolic extract of heal all exhibited antiestrogenic activity. Specifically, a reduction in alkaline phosphatase activity and cell proliferation in response to estrogen in a dose-dependent manner was observed. The expression of an estrogen-induced protein was blocked in the cell line both by a standard antiestrogen compound and by the heal all extract (Collins et al. 2009). 

Estrogens stimulate cellular proliferation, induce RNA and protein synthesis of uterine endometrium and the fibrous connective tissue framework for ovaries, and increase the size of the cells. This effect leads to the growth and regeneration of the endometrial layer and spinal arterioles, and increase in the number and size of endometrial glands. Under the influence of estrogen, vaginal mucosa becomes thicker, as cervical mucus becomes thinner (85,86). 

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