Effects of tamoxifen on growth and apoptosis of estrogen-dependent and -independent human breast cancer cells

Abstract

TAM induces typical apoptosis in ER(+) or ER(-) human breast cancer cells. TAM induction of apoptosis in MCF-7 cells involves the estrogen receptor, and requires the synthesis of new protein and mRNA. TAM induction of apoptosis in MDA-231 cells depends primarily on protein synthesis. TAM-induced cytotoxicity and DNA damage appear to be explained in part by the induction of apoptosis.

Relationship between tamoxifen-induced transforming growth factor beta 1 expression, cytostasis and apoptosis in human breast cancer cells

“…The results of this study show a good correlation between TAM induction of TGF-P1 and cell cycle blockade in GI/Go, which may at least partially explain the cytostatic effects of TAM. The time course of TAM-induced alterations in TGF-P3 expression and cell cycle kinetics was similar to the time course of TAMinduced apoptosis seen in our previous study (Perry et al, 1995). TAM induction of TGF-P1 correlated strongly with internucleosomal DNA cleavage.…”

“…Although MCF-7 cells are slightly more sensitive to TAMinduced apoptosis (Perry et al, 1995), in this study we found no significant difference between the two cells lines in the degree or time course of TAM induction of TGF-pf. Oestrogen inhibits TAM-induced cytostasis and apoptosis in MCF-7 cells but not in MDA-231 cells, suggesting that TAM induces apoptosis via both ER-dependent and ER-independent pathways (Perry et al, 1995).…”

“…TAM induction of TGF-1,B precedes apoptosis, since TGF-P, mRNA was induced by 6-12 h and DNA cleavage and apoptosis in our previous study was not observed until 12-24h (Table I) (Perry et al, 1995). In the present study addition of anti-TGF-P1 antibody inhibited TAM-induced internucleosomal DNA cleavage (Figure 6), a strong indication that induction of TGF-PJ by TAM triggers apoptosis.…”

“…Since TGF-PI is rapidly degraded, with the preform having a half-life of 2 h and the active form only 2 min, active synthesis is required for this protein to be expressed (Wakefield et al, 1987). Recent work in our laboratory has shown that TAM can induce growth stimulation at low dose or growth inhibition and apoptosis at higher doses in either ER( + ) MCF-7 or ER( -) MDA-231 human breast cancer cells (Table I; Perry et al, 1995). TAM for 6 h resulted in a slight but non-significant decrease of TGF-13I protein, accompanied by a slight increase in cell growth (Table I) and an increase in the number of cells entering S-phase (Table II) certain models can increase death-associated mRNAs (Owens et al, 1991).…”

Activation of AKT/PKB in breast cancer predicts a worse outcome among endocrine treated patients

“…These mechanisms, mainly involved in cell proliferation, may coexist with those affecting cell death. Increasing amount of evidence indicates that the mechanisms whereby drugs such as the LHRH analogues and tamoxifen exert the cytotoxic action also include apoptosis (Perry et al, 1995;Imai and Tamaya, 2000). Therefore, factors involved in the apoptotic failure may also contribute to the anti-oestrogen resistance.…”