BACKGROUND Tamoxifen (TAM) is a nonsteroidal antiestrogen that has been widely used in the treatment of breast cancer through its anti-estrogen activity. Recent studies show that TAM is cytotoxic to both estrogen receptor (ER)-positive and ER-negative cells via the induction of apoptosis. However, the molecular mechanisms of this effect are not well understood. In the present study, we investig...

The major metabolites of tamoxifen (tam) formed by animal and human liver microsomes are mono-N-demethylated tam, 4-hydroxy-tam (4-OH-tam), and tam-N-oxide. The N-desmethylated-tam and 4-OH-tam are formed by P450s, whereas the N-oxide is primarily formed by flavin-containing monooxygenase. Because 4-OH-tam is a highly potent antiestrogen (and possibly is the active anticancer tam metabolite) an...

In Arabidopsis, loss-of-function mutations in the A-type cyclin CYCA1;2/Tardy Asynchronous Meiosis (TAM) gene lead to the production of abnormal meiotic products including triads and dyads. Here we report that overexpression of TAM by the ASK1:TAM transgene also led to the production of triads and dyads in meiosis, as well as shriveled seeds, in a dominant fashion. However, the partial loss-of-...

Tamoxifen (TAM) is a selective estrogen receptor modulator widely used in the prevention and treatment of breast cancer. A major mode of metabolism of the major active metabolites of TAM, 4-OH-TAM and endoxifen, is by glucuronidation via the UDP-glucuronosyltransferase (UGT) family of enzymes. To examine whether polymorphisms in the UGT enzymes responsible for the glucuronidation of active TAM ...

Tamoxifen (TAM), used as the endocrine therapy of choice for breast cancer, undergoes metabolism primarily forming N-desmethyltamoxifen, 4-hydroxytamoxifen, alpha-hydroxytamoxifen, and tamoxifen-N-oxide (TNO). Our earlier studies demonstrated that flavin-containing monooxygenases (FMOs) catalyze the formation of TNO. The current study demonstrates that human FMO1 and FMO3 catalyze TAM N-oxidati...

PURPOSE Tamoxifen (Tam) is the most prescribed hormonal agent for treatment of estrogen receptor α (ERα)-positive breast cancer patients. Using microarray analysis, we observed that metastatic breast tumors resistant to Tam therapy had elevated levels of Dicer. EXPERIMENTAL DESIGN We overexpressed Dicer in ERα-positive MCF-7 human breast cancer cells and observed a concomitant increase in exp...

Generally speaking, technology acceptance model (TAM, Davis, et al., 1989; Davis, 1989) is a successful model and prior studies have explored the TAM from different perspectives and many antecedents have been identified. However, the overview of TAM shows that the explanatory power of TAM is limited. Furthermore, more and more inconsistencies in results appeared along with the development of TA...

To assess the effects of chronic administration of tamoxifen (TAM) and toremifene (TOR) on genetic damage related to carcinogenesis, we measured DNA adduct formation by (32)P-postlabeling in liver, kidney, and uterus of Fischer rats given TAM or TOR in the diet for 18 months. TAM induced high levels of DNA adducts in the liver in a dose-dependent manner. The total adduct levels were 3000 +/- 87...

The goals of this clinical trial involving postmenopausal women with metastatic breast cancer were to: (a) examine the effects of letrozole on tamoxifen (TAM) pharmacokinetics; (b) examine estrogen suppression in patients receiving TAM plus letrozole; and (c) evaluate tolerability, toxicity, objective response, and time to progression for the combination. Postmenopausal women with measurable or...

BACKGROUND Tamoxifen (TAM) is generally considered the hormonal agent of choice for postmenopausal women with hormone receptor positive breast carcinoma. The somatostatin analogues, including octreotide, have demonstrated inhibition of breast carcinoma cell lines and multiple endocrinologic actions, including reduction of insulin-like growth factor I (IGF-I), a potent mitogen for breast carcino...