What question did this study set out to answer?

To identify downstream target genes regulated by constitutive Stat3 signaling that mediate survival and apoptosis resistance in human breast cancer.

January 1, 2006Clinical Cancer ResearchOpen Access

Persistent Activation of Stat3 Signaling Induces Survivin Gene Expression and Confers Resistance to Apoptosis in Human Breast Cancer Cells

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To identify downstream target genes regulated by constitutive Stat3 signaling that mediate survival and apoptosis resistance in human breast cancer.
Treated human MDA-MB-435s breast cancer cells with Stat3 antisense oligonucleotides and performed Affymetrix GeneChip microarray profiling.
Assessed direct promoter binding and transcriptional regulation using Survivin promoter reporter assays and chromatin immunoprecipitation.
Evaluated Stat3 activation and Survivin protein expression by immunohistochemistry in primary tumor specimens from high-risk, chemotherapy-resistant breast cancer patients.
Microarray analysis, promoter assays, and chromatin immunoprecipitation established that Stat3 directly binds the Survivin promoter to drive its transcription.
Targeted inhibition of either Stat3 signaling or Survivin expression suppressed protein levels and induced apoptosis in cultured breast cancer cells.
Elevated Survivin expression correlated significantly with increased Stat3 activity in primary tumor tissues from chemotherapy-resistant patients (P = 0.001).

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Implication

Translational study demonstrates Stat3-driven Survivin expression in chemoresistant breast cancer, indicating a critical mechanism of apoptosis resistance.

Cite This Study

Gritsko et al. (2006) studied this question.

synapsesocial.com/papers/6a7bb65d073f483584df8800 https://doi.org/10.1158/1078-0432.ccr-04-1752

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Implication

Translational study demonstrates Stat3-driven Survivin expression in chemoresistant breast cancer, indicating a critical mechanism of apoptosis resistance.

Persistent Activation of Stat3 Signaling Induces Survivin Gene Expression and Confers Resistance to Apoptosis in Human Breast Cancer Cells

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Discussion

Implication

Cite This Study

Persistent Activation of Stat3 Signaling Induces Survivin Gene Expression and Confers Resistance to Apoptosis in Human Breast Cancer Cells

Key Points

Discussion

Implication

Cite This Study

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