Resistance to tamoxifen is observed in half of the recurrences in breast cancer, where the anti-estrogen tamoxifen acquires agonistic properties for transactivating estrogen receptor alpha (ERalpha). In a previous study, we showed that protein kinase A (PKA)-mediated phosphorylation of serine 305 (S305) of ERalpha results in resistance to tamoxifen. Now, we demonstrate that phosphorylation of S...

Tamoxifen is commonly used in the management of patients with breast cancer. Clinical trials of tamoxifen involving over 75,000 patients demonstrate an improved recurrence-free and overall survival benefit in both pre- and post-menopausal women. Large-scale trials also are evaluating the role of tamoxifen as a chemopreventive agent in women considered to be at high risk for developing breast ca...

ZR-75-1 human mammary cancer cells can be grown in serum-free medium in an estradiol- and tamoxifen-sensitive manner. Growth occurs both in monolayer and suspension culture, although serum is necessary during the initial plating of the cells in monolayer culture. Optimal stimulation of proliferation by estradiol occurs at 10(-8) and 10(-9) M. Tamoxifen alone weakly stimulated growth in a dose-d...

Epidemiological and experimental evidences strongly support the role of estrogens in breast tumor development. Both estrogen receptor (ER)-dependent and ER-independent mechanisms are implicated in estrogen-induced breast carcinogenesis. Tamoxifen, a selective estrogen receptor modulator is widely used as chemoprotectant in human breast cancer. It binds to ERs and interferes with normal binding ...

Estrogen-dependent breast cancer is often treated with the aromatase inhibitors or estrogen receptor (ER) antagonists. Tamoxifen as a major ER antagonist is usually used to treat those patients with ERα-positive breast cancer. However, a majority of patients with ERα positive fail to respond to tamoxifen due to the presence of intrinsic or acquired resistance to the drug. Altered expression and...

OBJECTIVES Physical appearance has significant importance psychologically and socially, with skin and hair being of prime relevance. Effective ingredients that modulate melanin synthesis are of growing interest. Tamoxifen, a widely used selective oestrogen receptor modulator, SERM, was described occasionally in medical case reports as causing grey hair repigmentation. This work aimed to study, ...

Tamoxifen, a partial estrogen receptor antagonist, is part of the standard treatment of both primary and advanced breast cancers. However, significant proportions of breast cancers are either de novo resistant or develop tamoxifen resistance during the course of treatment through mechanisms which have been only partly characterized. We have previously found that high vascular endothelial growth...

PURPOSE Vascular endothelial growth factor (VEGF) is a key angiogenic factor mediating neovascularization. Soluble VEGF receptor 1 (sVEGFR-1) is an intrinsic negative counterpart of VEGF signaling and the ratio of sVEGFR-1 to VEGF has been shown to be a prognostic factor. Estrogen-bound estrogen receptor enhances VEGF expression, providing a common link between these signaling pathways that may...

HER2/neu (erbB-2) overexpression has been causally associated with tamoxifen resistance in human breast cancer cells. Forced expression of HER2 in MCF-7 breast cancer cells resulted in mitogen-activated protein kinase (MAPK) hyperactivity and tamoxifen resistance. Inhibition of HER2 and MAPKs with AG1478 and U0126, respectively, as well as dominant-negative MEK-1/2 constructs restored the inhib...