The antiestrogen tamoxifen is important in the treatment of hormone-dependent breast cancer, although development of resistance is inevitable. To unravel the molecular mechanisms of antiestrogen resistance, a search for involved genes was initiated. Retrovirus-mediated insertional mutagenesis was applied to human ZR-75-1 breast cancer cells. Infected cells were subjected to tamoxifen selection ...

The antiestrogen tamoxifen has been used in the treatment of hormone-responsive breast cancer for over a decade. The loss of estrogen receptor (ER) expression is the most common mechanism for de novo antiestrogen resistance. Wilms’ tumor 1 suppressor gene (WT1) is a clinically useful marker that is associated with poor prognosis in breast cancer patients; its high level expression is frequently...

It is prevailingly thought that the antiestrogens tamoxifen and ICI 182, 780 are competitive antagonists of the estrogen-binding site of the estrogen receptor-alpha (ER-α). However, a plethora of evidence demonstrated both antiestrogens exhibit agonist activities in different systems such as activation of the membrane-initiated signaling pathways. The mechanisms by which antiestrogens mediate e...

The antiestrogen tamoxifen has been used in the treatment of hormone-responsive breast cancer for over a decade. The loss of estrogen receptor (ER) expression is the most common mechanism for de novo antiestrogen resistance. Wilms' tumor 1 suppressor gene (WT1) is a clinically useful marker that is associated with poor prognosis in breast cancer patients; its high level expression is frequently...

This study identifies macroautophagy as a key mechanism of cell survival in estrogen receptor-positive (ER+) breast cancer cells undergoing treatment with 4-hydroxytamoxifen (4-OHT). This selective ER modifier is an active metabolite of tamoxifen commonly used for the treatment of breast cancer. Our study provides the following key findings: (a) only 20% to 25% of breast cancer cells treated wi...

Somatic mutations in the estrogen receptor alpha (ERα) gene (ESR1), especially Y537S and D538G, have been linked to acquired resistance to endocrine therapies. Cell-based studies demonstrated that these mutants confer ERα constitutive activity and antiestrogen resistance and suggest that ligand-binding domain dysfunction leads to endocrine therapy resistance. Here, we integrate biophysical and ...

The rat lymphoma cell line Nb2 is highly prolactin responsive in terms of growth. Estrogens are without effect in these cells that lack the estrogen receptor. The growth stimulation by lactogenic hormones is effectively inhibited by antiestrogens, such as tamoxifen and nafoxidine, at concentrations as low as 10(-10) M. The growth inhibition is partially reversed by replacement of the antiestrog...

We investigated the effects of estradiol on bioactive luteinizing hormone (LH) release in normal men using two complementary strategies: (i) steady state intravenous infusions of estradiol at its endogenous production rate, and (ii) oral administration of the antiestrogen, tamoxifen HCl. Immunoreactive and biologically active LH were monitored by radioimmunoassay and the rat interstitial cell t...

Estrogens are required for the proliferation of hormone dependent breast cancer cells, making estrogen receptor (ER) positive tumors amenable to endocrine therapies such as antiestrogens. However, resistance to these agents remains a significant cause of treatment failure. We previously demonstrated that inactivation of the retinoblastoma protein (pRb) family tumor suppressors causes antiestrog...