The Forkhead Box M1 Protein Regulates the Transcription of the Estrogen Receptor α in Breast Cancer Cells

Madureira, Patrícia A.; Varshochi, Rana; Constantinidou, Demetra; Francis, Richard E.; Coombes, R. Charles; Yao, KM; Lam, Eric W.‐F.

doi:10.1074/jbc.m603906200

Cited by 157 publications

(142 citation statements)

References 33 publications

(17 reference statements)

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“…Cell viability was measured using WST-1, an antiproliferative assay. MCF-7 and ZR-75-30 cells are positively expressed ERa whereas MDA-MB-231 and SK-BR-3 cell are not (38)(39)(40)(41)(42)(43). HMQ1611 decreased the cell viabilities of the 4 types of cancer cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

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A Novel Taspine Derivative, HMQ1611, Inhibits Breast Cancer Cell Growth via Estrogen Receptor α and EGF Receptor Signaling Pathways

Zhan

Zhang

Liu

et al. 2012

Cancer Prevention Research

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Breast cancer is a common cancer with a leading cause of cancer mortality in women. Currently, the chemotherapy for breast cancer is underdeveloped. Here, we report a novel taspine derivative, HMQ1611, which has anticancer effects using in vitro and in vivo breast cancer models. HMQ1611 reduced cancer cell proliferation in four human breast cancer cell lines including MDA-MB-231, SK-BR-3, ZR-75-30, and MCF-7. HMQ1611 more potently reduced growth of estrogen receptor a (ERa)-positive breast cancer cells (ZR-75-30 and MCF-7) than ERa-negative cells (MDA-MB-231 and SK-BR-3). Moreover, HMQ1611 arrested breast cancer cell cycle at S-phase. In vivo tumor xenograft model, treatment of HMQ1611 significantly reduced tumor size and weight compared with vehicles. We also found that HMQ1611 reduced ERa expression and inhibited membrane ERa-mediated mitogenactivated protein kinase (MAPK) signaling following the stimulation of cells with estrogen. Knockdown of ERa by siRNA transfection in ZR-75-30 cells attenuated HMQ1611 effects. In contrast, overexpression of ERa in MDA-MB-231 cells enhanced HMQ1611 effects, suggesting that ERa pathway mediated HMQ1611 0 s inhibition of breast cancer cell growth in ERa-positive breast cancer. HMQ1611 also reduced phosphorylation of EGF receptor (EGFR) and its downstream signaling players extracellular signal-regulated kinase (ERK)1/2 and AKT activation both in ZR-75-30 and MDA-MB-231 cells. These results showed that the novel compound HMQ1611 had anticancer effects, and partially via ERa and/or EGFR signaling pathways, suggesting that HMQ1611 may be a potential novel candidate for human breast cancer intervention. Cancer Prev Res; 5(6); 864-73. Ó2012 AACR.

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Section: Resultsmentioning

confidence: 99%

“…In our laboratory, cell morphology, growth curve, and mycoplasma contamination were regularly checked to ensure the absence of contamination during the culture. MCF-7 and ZR-75-30 are ERa-positive expression cell lines (38)(39)(40)(41). SK-BR-3 and MDA-MB-231 are ERa-negative cell lines (42,43 …”

Section: Cell Linesmentioning

confidence: 99%

A Novel Taspine Derivative, HMQ1611, Inhibits Breast Cancer Cell Growth via Estrogen Receptor α and EGF Receptor Signaling Pathways

Zhan

Zhang

Liu

et al. 2012

Cancer Prevention Research

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“…FoxM1 has a critical function in G2 and M transition by regulating the expression of various G2/M cell cycle regulatory genes, including polo-like kinase, cyclin B, cyclin A, CDC25B and CDC2 (Wang et al, 2002a, b;Yoshida et al, 2007), and loss of FoxM is associated with G2/M checkpoint arrest and loss of mitotic spindle integrity (Laoukili et al, 2005;Wonsey and Follettie, 2005). Overexpression of FoxM1 through chromosomal amplification or the activation of transcription, for example, through Gli-1 is associated with the development and progression of many cancer types, including cancers of the breast, liver, prostate, brain and lung (Teh et al, 2002;Kalinichenko et al, 2004;Kalin et al, 2006;Kim et al, 2006;Liu et al, 2006;Madureira et al, 2006). Other mechanisms of interaction may exist between FoxM1 and FoxO3a.…”

Section: Foxo Transcriptional Network and Cell Cyclementioning

confidence: 99%

Many forks in the path: cycling with FoxO

2008

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FoxO transcription factors are an evolutionary conserved subfamily of the forkhead transcription factors, characterized by the forkhead DNA-binding domain. FoxO factors regulate a number of cellular processes involved in cell-fate decisions in a cell-type-and environment-specific manner, including metabolism, differentiation, apoptosis and proliferation. A key mechanism by which FoxO determines cell fate is through regulation of the cell cycle machinery, and as such the cellular consequence of FoxO deregulation is often manifested through perturbation of the cell cycle. Consequently, the deregulation of FoxO factors is implicated in the development of numerous proliferative diseases, in particular cancer.

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“…Western Blot Analysis and Antibodies Cells were lysed and SDS-PAGE was done as described previously (19). The antibodies against FOXM1 (H-300), h-tubulin (H-235), CDC25b (C-20), Polo-like kinase-1 (F-8), and cyclin D1 (CRI-24) were purchased from Santa Cruz Biotechnology (Autogen Bioclear).…”

Section: Plasmidsmentioning

confidence: 99%

“…The FOXM1 expression vector contains a full-length FOXM1 cDNA cloned into pCDNA3.1 (Invitrogen) that has been described previously in ref. 19. The FOXO3a promoter was amplified using primers 5 ¶-CTAGCTAGCTCTCTCTCCTTCCTTAGAATTT-TACTCG- ¶ and 5 ¶-GCACACAGATATTGAAACACGAC-GAGAGCTCGCC-3 ¶ from genomic DNA extracted from MCF-7 cells.…”

Section: Plasmidsmentioning

confidence: 99%

Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression

Kwok

Myatt

Marson

et al. 2008

Molecular Cancer Therapeutics

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224

203

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Elevated expression or activity of the transcription factor forkhead box M1 (FOXM1) is associated with the development and progression of many malignancies, including breast cancer. In this study, we show that the thiazole antibiotic thiostrepton selectively induces cell cycle arrest and cell death in breast cancer cells through down-regulating FOXM1 expression. Crucially, our data show that thiostrepton treatment reduced FOXM1 expression in a time-and dose-dependent manner, independent of de novo protein synthesis and predominantly at transcriptional and gene promoter levels. Our results indicate that thiostrepton can induce cell death through caspase-dependent intrinsic and extrinsic apoptotic pathways as well as through caspase-independent death mechanisms, as observed in MCF-7 cells, which are deficient of caspase-3 and caspase-7. Cell cycle analysis showed that thiostrepton induced cell cycle arrest at G 1 and S phases and cell death, concomitant with FOXM1 repression in breast cancer cells. Furthermore, thiostrepton also shows efficacy in repressing breast cancer cell migration, metastasis, and transformation, which are all downstream functional attributes of FOXM1. We also show that overexpression of a constitutively active FOXM1 mutant, #N-FOXM1, can abrogate the antiproliferative effects of thiostrepton. Interestingly, thiostrepton has no affect on FOXM1 expression and proliferation of the untransformed MCF-10A breast epithelial cells. Collectively, our data show that FOXM1 is one of the primary cellular targets of thiostrepton in breast cancer cells and that thiostrepton may represent a novel lead compound for targeted therapy of breast cancer with minimal toxicity against noncancer cells.

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The Forkhead Box M1 Protein Regulates the Transcription of the Estrogen Receptor α in Breast Cancer Cells

Abstract: Together with the chromatin immunoprecipitation and biotinylated oligonucleotide pulldown data, the co-immunoprecipitation results also suggest the possibility that FoxM1 and FoxO3a cooperate to regulate ER␣ gene transcription.

Cited by 157 publications

References 33 publications

A Novel Taspine Derivative, HMQ1611, Inhibits Breast Cancer Cell Growth via Estrogen Receptor α and EGF Receptor Signaling Pathways

A Novel Taspine Derivative, HMQ1611, Inhibits Breast Cancer Cell Growth via Estrogen Receptor α and EGF Receptor Signaling Pathways

Many forks in the path: cycling with FoxO

Thiostrepton selectively targets breast cancer cells through inhibition of forkhead box M1 expression

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