Dataset Information

Acquisition of Letrozole Resistance Through Activation of the p38/MAPK Signaling Cascade.

ABSTRACT:

Background/aim

Previous reports identified a global proteomic signature of estrogen-independent letrozole resistant breast cancer cells, however, it remains unclear how letrozole-resistance is impacted when cells remain estrogen receptor positive (ER+).

Materials and methods

To capture the protein expression profile associated with ER+ Aromatase inhibitor (AI) resistance, a global proteomic analysis was conducted using the letrozole-sensitive (T47Darom cells) and letrozole-resistant cells (T47DaromLR cells). To examine the molecular features associated with this phenotype Kaplan- Meier analysis, phospho-antibody arrays, proliferation and apoptosis assays were conducted.

Results

MAP3K6 was up-regulated in the T47DaromLR cells by 3.2-fold (p<0.01) which was associated with a decrease in relapse-free survival among breast cancer patients (p=0.0019). Members of the MAPK/p38 pathway (i.e., phospho-MKK6, phospho-p38, phospho-RSK1, phospho-RSK2, and p70S6K MAPK) were also increased in the T47DaromLR cells, while inhibiting p38 led to decreased proliferation and induction of apoptosis.

Conclusion

Activation of the p38/MAPK pathway leads to ER+ AI-resistance.

SUBMITTER: Walker RR

PROVIDER: S-EPMC8556662 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Acquisition of Letrozole Resistance Through Activation of the p38/MAPK Signaling Cascade.

Walker Rashidra R RR Gallegos Karen M KM Bratton Melyssa R MR Lemieux Kitani P KP Zhang Kun K Wang Guangdi G Davidson A Michael AM Tilghman Syreeta L SL

Anticancer research 20210201 2

<h4>Background/aim</h4>Previous reports identified a global proteomic signature of estrogen-independent letrozole resistant breast cancer cells, however, it remains unclear how letrozole-resistance is impacted when cells remain estrogen receptor positive (ER+).<h4>Materials and methods</h4>To capture the protein expression profile associated with ER+ Aromatase inhibitor (AI) resistance, a global proteomic analysis was conducted using the letrozole-sensitive (T47Darom cells) and letrozole-resista ...[more]

PMID: 33517263

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Dataset Information

Acquisition of Letrozole Resistance Through Activation of the p38/MAPK Signaling Cascade.

Background/aim

Materials and methods

Results

Conclusion

Publications

Acquisition of Letrozole Resistance Through Activation of the p38/MAPK Signaling Cascade.

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