Tamoxifen

TAM treatment inhibits significantly MCF7 cell proliferation. Low doses of TAM are able to induce structural chromosomal aberrations (deletions, isochromosomes, translocations, and dicentric chromosomes) in both ER+ and ER- breast cancer cells. This genotoxic effect is higher in those cell lines with HER2 gene amplification^[2]. Whereas TAM at lower concentrations (0.1-1 μM) induces a cell-cycle arrest, pharmacological concentrations (above 5 μM) of TAM have been found to induce apoptosis of breast cancer cells. 5 μM TAM rapidly induced sustained activation of ERK1/2 in ER-positive breast cancer cell lines (MCF-7 and T47D)^[3]

Tamoxifen (TAM) is widely used for both treatment and prevention of breast cancer. However, it is also carcinogenic in human uterus and rat liver^[2]. Tm-inducible Cre-loxP systems are being used in broad areas of research and are providing important biologic insights in tissue development, maintenance, and function. Tamoxifen-induced nuclear localization of Cre recombinase is time- and dose-dependent. Higher doses of tamoxifen induce recombination weeks following administration and Lower doses of tamoxifen induce recombination up to one week following administration. Duration of tamoxifen-induced gene recombination is also dose-dependent. Administration of high Tm doses leads to extended CreER nuclear localization. Tm treatment induces side effects that may have physiologic consequences in Tm-inducible models^[4].

• Cell lines

  MCF7 and T47D

• Concentrations

  10^-6 mol/L

• Incubation Time

  24, 48, and 96 h

• Method

  48 h before the addition of E2 and TAM, cells were washed with 5 mL phosphate-buffered saline (PBS) and then switched to phenol red-free RPMI-1640 containing 10% charcoal-stripped FBS. E2 and TAM were dissolved in absolute ethanol and diluted in the media at 10^-8 mol/L and 10^-6 mol/L, respectively, and then added to the culture medium at 24, 48, and 96 h.

• Animal Models

  Pdx1PB-CreER^Tm mice

• Dosages

  --

• Administration

  s.c.