Glucocorticoid and Growth Factor Synergism Requirement for <i>Notch4</i> Chromatin Domain Activation

Wu, Jing; Bresnick, Emery H.

doi:10.1128/mcb.02152-06

Cited by 22 publications

(14 citation statements)

References 82 publications

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“…The Notch-4 promoter has activator protein-1 (AP-1)-binding sites (Figure 3c) and is regulated by AP-1 subunits in other systems. 23, 24 Elevated AP-1 activity in T47D:A18/PKCα cells has been reported. 14 T47D:A18/PKCα cells express higher levels of AP-1 subunits and have higher basal AP-1 reporter activity than controls (Figure 3c).…”

Section: Resultsmentioning

confidence: 96%

Crosstalk between PKCα and Notch-4 in endocrine-resistant breast cancer cells

et al. 2013

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The Notch pathway is functionally important in breast cancer. Notch-1 has been reported to maintain an estrogen-independent phenotype in estrogen receptor α (ERα)+ breast cancer cells. Notch-4 expression correlates with Ki67. Notch-4 also plays a key role in breast cancer stem-like cells. Estrogen-independent breast cancer cell lines have higher Notch activity than estrogen-dependent lines. Protein kinase Cα (PKCα) overexpression is common in endocrine-resistant breast cancers and promotes tamoxifen (TAM)-resistant growth in breast cancer cell lines. We tested whether PKCα overexpression affects Notch activity and whether Notch signaling contributes to endocrine resistance in PKCα-overexpressing breast cancer cells.Analysis of published microarray data from ERα+ breast carcinomas shows that PKCα expression correlates strongly with Notch-4. Real-time reverse transcription PCR and immunohistochemistry on archival specimens confirmed this finding. In a PKCα-overexpressing, TAM-resistant T47D model, PKCα selectively increases Notch-4, but not Notch-1, expression in vitro and in vivo. This effect is mediated by activator protein-1 (AP-1) occupancy of the Notch-4 promoter. Notch-4 knockdown inhibits estrogen-independent growth of PKCα-overexpressing T47D cells, whereas Notch-4IC expression stimulates it. Gene expression profiling shows that multiple genes and pathways associated with endocrine resistance are induced in Notch-4IC- and PKCα-expressing T47D cells. In PKCα-overexpressing T47D xenografts, an orally active γ-secretase inhibitor at clinically relevant doses significantly decreased estrogen-independent tumor growth, alone and in combination with TAM. In conclusion, PKCα overexpression induces Notch-4 through AP-1. Notch-4 promotes estrogen-independent, TAM-resistant growth and activates multiple pathways connected with endocrine resistance and chemoresistance. Notch inhibitors should be clinically evaluated in PKCα- and Notch-4-overexpressing, endocrine-resistant breast cancers.

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Section: Resultsmentioning

confidence: 96%

Crosstalk between PKCα and Notch-4 in endocrine-resistant breast cancer cells

et al. 2013

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“…73 Cortisol and dexamethasone combined with FGF-2 strongly induced Notch4 expression. 74 However, Notch4 activation in endothelial cells in vivo may inhibit angiogenesis. 75 Finally, fibroblast growth and angiogenesis are not independent phenomena, but it has been highlighted that fibroblasts were necessary for formation of capillary-like structures when using the human umbilical vein endothelial cells (HUVEC) model.…”

Section: Discussionmentioning

confidence: 99%

Effect of Preoperative Single-Dose Corticosteroid Administration on Postoperative Morbidity Following Esophagectomy

Engelman

Maeyens

2010

Journal of Gastrointestinal Surgery

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“…Expression of Jagged-1 was reported to be increased by nuclear factor (NF)-kB (Bash et al, 1999). Transcription of Notch-4 in endothelial cells is induced by AP-1 (Wu et al, 2005) and the glucocorticoid receptor (Wu and Bresnick, 2007), which uncharacteristically act synergistically at the Notch-4 promoter. Notch-1 has been reported to upregulate its own transcription (Deftos et al, 1998) and that of Notch-4 (Weijzen et al, 2002).…”

Section: Targeting Notch In Cancermentioning

confidence: 99%