Tamoxifen induces p21WAF1 and p27KIP1 expression in estrogen receptor-negative lung cancer cells

Lee, Te-Hsiu; Chuang, Li‐Yeh; Hung, Wen‐Chun

doi:10.1038/sj.onc.1202755

Cited by 29 publications

(17 citation statements)

References 46 publications

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“…KIP1 in an ER-independent manner (Lee et al, 1999). In this study, we show that Tam activates p21 WAF1 expression through Sp1-binding site located between bp 783 and 774 in the p21 WAF1 promoter.…”

Section: Discussionmentioning

confidence: 74%

“…KIP1 (Lee et al, 1999). We found that upregulation of CDKIs in lung cancer cells by Tam led to reduced activity of cyclin E-associated kinases, accumulation of hypophosphorylated retinoblastoma (Rb) protein and G1 growth arrest in these cells.…”

mentioning

confidence: 90%

“…Cells were transfected with 2 mg of plasmids with the LipofectAMINE method as described previously (Lee et al, 1999). Cells were pretreated with inhibitors for 1 h and were incubated with vehicle (0.2% ethanol) or Tam (10 mM) for 24 h, and luciferase activities were assayed.…”

Section: Luciferase Assaysmentioning

confidence: 99%

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Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

2000

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Section: Discussionmentioning

confidence: 74%

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confidence: 90%

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Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

2000

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“…Suppression of tumor growth by 4OH-Tam has been associated with downmodulation of cyclin D1 (Jang et al, 2001). 4OH-Tam induces the expression of p21 Waf1 and p27 Kip1 , which block the activating effect of cyclin D1 (Lee et al, 1999b). In this report, we have tested the ability of 4-HPR and 4OH-Tam to inhibit the growth of rhabdoid cells in vitro and tumors in vivo.…”

Section: Introductionmentioning

confidence: 99%

Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors

et al. 2005

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Rhabdoid tumors (RTs) are aggressive and currently incurable pediatric malignancies. INI1/hSNF5 is a tumor suppressor biallelically inactivated in RTs. Our previous studies have indicated that cyclin D1 is a key downstream target of INI1/hSNF5 and genesis and/or survival of RTs in vivo is critically dependent on the presence of cyclin D1. In this report, we have tested the hypothesis that therapeutic targeting of cyclin D1 is an effective means of treating RTs. We found that RNA interference of cyclin D1 in rhabdoid cells was sufficient to induce G1 arrest and apoptosis. Furthermore, we found that pharmacological intervention with low micromolar concentrations of N-(4-hydroxyphenyl)retinamide (4-HPR), which downmodulates cyclin D1, induced G1 arrest and apoptosis in rhabdoid cell lines. 4-HPR in combination with 4-hydroxy-tamoxifen (4OH-Tam), synergistically inhibited survival as well as anchorage-dependent and -independent growth of rhabdoid cells and caused synergistic induction of cell cycle arrest and apoptosis. 4-HPR and tamoxifen exhibited synergistic growth inhibition of RTs in xenograft models in vivo. The effects of combination of drugs were correlated to the depletion of cyclin D1 levels both in in vitro and in vivo tumor models. These results demonstrate that 4-HPR and tamoxifen are effective chemotherapeutic agents for RTs. We propose that downmodulation of cyclin D1 is a novel and effective therapeutic strategy for RTs.

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“…WAF1 and p27 KIP1 , combined with a reduction in cyclin D1 protein that acts to inhibit cyclin D/CDK4 and cyclin E/CDK2 activity and arrest cell cycle progression (Wilcken et al 1997, Lee et al 1999, DoisneauSixou et al 2003. Interestingly, over-expression of cyclin D1 (Wilcken et al 1997) or cyclin E can alleviate tamoxifen inhibition of MCF-7 cells in culture (Dhillon & Mudryj 2002).…”

Section: Introductionmentioning

confidence: 99%

The molecular basis of tamoxifen induction of mouse uterine epithelial cell proliferation

Zhang

McElrath²,

Tong³

et al. 2005

Journal of Endocrinology

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Tamoxifen, a selective estrogen modulator (SERM) that has found clinical utility in the treatment of breast cancer, is an antagonist in the breast and an agonist in the uterus. These agonist actions in the uterus lead to an increased risk of endometrial cancer. In this study in mice we have analyzed the mechanism of action of tamoxifen in inducing cell proliferation in the uterine luminal epithelia. Tamoxifen induces a wave of DNA synthesis in these epithelial cells with kinetics similar to those seen after 17 -estradiol (E 2 ) treatment. However, by these criteria of mitogenicity, it is much less potent and never achieves full estrogenicity. This uterine epithelial cell proliferation is preceded by the mobilization of cyclin D1 from the cytoplasm to the nucleus which, together with CDK4, phosphorylates members of the Rb-retinoblastoma family of proteins, pRb and p107. Subsequent to this initial nuclear accumulation of cyclin D1, cyclin E and then cyclin A are induced that, together with the activation of CDK2, results in enhanced cyclin E-and cyclin A-dependent CDK2 kinase activity and further phosphorylation of pRb and p107. These actions of tamoxifen parallel those of E 2 . Tamoxifen also induced the classical estrogen water imbibition response. However, in this it was more potent, producing a maximal response at doses that do not affect DNA synthesis. This suggests that the uterotropic response is not an accurate predictor of the compound's hyperplasia responses. We can conclude that, in its effects on proliferation, tamoxifen acts as a classical impeded estrogen and this suggests that the AF-1 transcription activation domain of the estrogen receptor that is activated upon both E 2 and tamoxifen binding to this receptor regulates these responses in the uterus.

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Tamoxifen induces p21WAF1 and p27KIP1 expression in estrogen receptor-negative lung cancer cells

Cited by 29 publications

References 46 publications

Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

Induction of p21WAF1 expression via Sp1-binding sites by tamoxifen in estrogen receptor-negative lung cancer cells

Targeting cyclin D1, a downstream effector of INI1/hSNF5, in rhabdoid tumors

The molecular basis of tamoxifen induction of mouse uterine epithelial cell proliferation

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