Cyclin D1 expression is dependent on estrogen receptor function in tamoxifen-resistant breast cancer cells

Kilker, Robin L.; Hartl, Michael; Rutherford, Tina M.; Planas-Silva, Maricarmen D.

doi:10.1016/j.jsbmb.2004.05.005

Cited by 53 publications

(47 citation statements)

References 58 publications

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“…MCF-7 cells were grown in phenol red-containing DMEM [Irvine Scientific (Santa Ana, CA) or Life Technologies/Invitrogen (Carlsbad, CA)] supplemented with 5% fetal bovine serum (FBS) and antibiotics. Tamoxifen-resistant variants were developed as described previously (29). The tamoxifen-resistant cells (MTR-3) were maintained in phenol red-free DMEM (Irvine Scientific or Life Technologies) supplemented with 5% charcoal/dextran-stripped FBS (CSS; Hyclone, Logan, UT), antibiotics, and 1 Amol/L tamoxifen (Sigma, St. Louis, MO).…”

Section: Methodsmentioning

confidence: 99%

“…We described previously development and characterization of a cell culture model of acquired resistance to tamoxifen derived from MCF-7 cells (29). In the present study, using a variant of MCF-7 cells whose proliferation is not inhibited by tamoxifen, we examined the requirement of cyclin D1 in growth of these human breast cancer cells that now can show tamoxifen-induced cell proliferation.…”

Section: Introductionmentioning

confidence: 97%

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Cyclin D1 Is Necessary for Tamoxifen-Induced Cell Cycle Progression in Human Breast Cancer Cells

Kilker

Planas-Silva²

2006

Cancer Research

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Despite the success of tamoxifen in treating hormoneresponsive breast cancer, its use is limited by the development of resistance to the drug. Understanding the pathways involved in the growth of tamoxifen-resistant cells may lead to new ways to treat tamoxifen-resistant breast cancer. Here, we investigate the role of cyclin D1, a mediator of estrogendependent proliferation, in growth of tamoxifen-resistant cells using a cell culture model of acquired resistance to tamoxifen. We show that tamoxifen and 4-hydroxytamoxifen (OHT) promoted cell cycle progression of tamoxifen-resistant cells after growth-arrest mediated by the estrogen receptor downregulator ICI 182,780. Down-regulation of cyclin D1 with small interfering RNA blocked basal cell growth of tamoxifenresistant cells and induction of cell proliferation by OHT. In addition, pharmacologic inhibition of phosphatidylinositol 3-kinase/Akt or mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 pathways decreased basal cyclin D1 expression and impaired OHT-mediated cyclin D1 induction and cell cycle progression. These findings indicate that cyclin D1 expression is necessary for proliferation of tamoxifen-resistant cells and for tamoxifen-induced cell cycle progression. These results suggest that therapeutic strategies to block cyclin D1 expression or function may inhibit development and growth of tamoxifen-resistant tumors.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Cyclin D1 Is Necessary for Tamoxifen-Induced Cell Cycle Progression in Human Breast Cancer Cells

Kilker

Planas-Silva²

2006

Cancer Research

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“…In mammary epithelial cells, the expression of cyclin D1 is regulated through the ER signaling (102). Cyclin D1 is a direct transcriptional target of estrogen signaling; thus, tamoxifen reduces cyclin D1 expression (103). In vitro sustained expression of cyclin D1 is evident in breast cancer cells during their acquisition of tamoxifen resistance, and downregulation of cyclin D1 with siRNA restored the sensitivity of these cells to tamoxifen (103).…”

Section: Cell Cycle Regulators Associated With Resistance To Tamoxifenmentioning

confidence: 99%

“…Cyclin D1 is a direct transcriptional target of estrogen signaling; thus, tamoxifen reduces cyclin D1 expression (103). In vitro sustained expression of cyclin D1 is evident in breast cancer cells during their acquisition of tamoxifen resistance, and downregulation of cyclin D1 with siRNA restored the sensitivity of these cells to tamoxifen (103). Cyclin D1 is one co-regulator, known to interact with ERα and can potentiate its transcriptional activity independently of estrogen and may not be inhibited by tamoxifen (104).…”

Section: Cell Cycle Regulators Associated With Resistance To Tamoxifenmentioning

confidence: 99%

Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (Review)

et al. 2014

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Abstract. Anti-estrogens such as tamoxifen are widely used in the clinic to treat estrogen receptor-positive breast tumors. Patients with estrogen receptor-positive breast cancer initially respond to treatment with anti-hormonal agents such as tamoxifen, but remissions are often followed by the acquisition of resistance and, ultimately, disease relapse. The development of a rationale for the effective treatment of tamoxifen-resistant breast cancer requires an understanding of the complex signal transduction mechanisms. In the present study, we explored some mechanisms associated with resistance to tamoxifen, such as pharmacologic mechanisms, loss or modification in estrogen receptor expression, alterations in co-regulatory proteins and the regulation of the different signaling pathways that participate in different cellular processes such as survival, proliferation, stress, cell cycle, inhibition of apoptosis regulated by the Bcl-2 family, autophagy, altered expression of microRNA, and signaling pathways that regulate the epithelial-mesenchymal transition in the tumor microenvironment. Delineation of the molecular mechanisms underlying the development of resistance may aid in the development of treatment strategies to enhance response and compromise resistance.

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“…Such ectopic cyclin D1 induction resulted in activation of cyclin D1-CDK4 complexes and entry of cells into S phase of cells indicating a reversal of cell cycle arrest. Later, it was shown that cyclin D1 was not endogenously up-regulated in tamoxifen-resistant MCF-7 cells, compared to parental MCF-7 cells (Kilker et al, 2004). It was up-regulated only on exposure to physiological levels of tamoxifen, suggesting a dependence of cyclin D1 expression on ER.…”

Section: Cell Cycle Regulation In Tamoxifen Resistant Breast Cancersmentioning

confidence: 99%

Cell Cycle Regulatory Proteins in Breast Cancer: Molecular Determinants of Drug Resistance and Targets for Anticancer Therapies

Ahmad¹,

Wang²,

Ali³

et al. 2012

Targeting New Pathways and Cell Death in Breast Cancer

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Cyclin D1 expression is dependent on estrogen receptor function in tamoxifen-resistant breast cancer cells

Cited by 53 publications

References 58 publications

Cyclin D1 Is Necessary for Tamoxifen-Induced Cell Cycle Progression in Human Breast Cancer Cells

Cyclin D1 Is Necessary for Tamoxifen-Induced Cell Cycle Progression in Human Breast Cancer Cells

Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (Review)

Cell Cycle Regulatory Proteins in Breast Cancer: Molecular Determinants of Drug Resistance and Targets for Anticancer Therapies

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