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Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes

Authors: Kruger, Dinja T; Opdam, Mark; Sanders, Joyce; van der Noort, Vincent; Boven, Epie; Linn, Sabine C;

Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes

Abstract

The phosphatidylinositol‐3‐kinase (PI3K) and mitogen‐activated protein kinase (MAPK) pathways are frequently activated in breast cancer. We recently demonstrated the importance of analyzing multiple proteins as read‐out for pathway activation in ER+/HER2− breast cancer, since single proteins are known to provide insufficient information. Here, we determined pathway activation in other primary breast cancer intrinsic subtypes derived from postmenopausal patients. Tumor blocks were recollected, and immunohistochemistry was performed using antibodies against PTEN, p‐AKT(Thr308), p‐AKT(Ser473), p‐p70S6K, p‐4EBP1, p‐S6RP(Ser235/236) and p‐ERK1/2, followed by unsupervised hierarchical clustering. In 32 ER+/HER2+, 37 ER−/HER2+ and 74 triple‐negative breast cancer patients, subgroups were identified with preferentially activated (A) and preferentially not activated (N) proteins. These subgroups likely reflect tumors with differences in biological behavior as well as treatment outcome.

Keywords

mitogen-activated protein kinase, Receptor, ErbB-2, Ribosomal Protein S6 Kinases, 70-kDa, Triple Negative Breast Neoplasms, Original Articles, triple-negative breast cancer, Biomarkers, Tumor, Humans, Female, Mitogen-Activated Protein Kinases, Phosphatidylinositol 3-Kinase, HER2-positive breast cancer, hierarchical clustering, phosphatidylinositol-3-kinase, Proto-Oncogene Proteins c-akt, Breast cancer intrinsic subtypes, Aged, Signal Transduction

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    selected citations
    These citations are derived from selected sources.
    This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    6
    popularity
    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Average
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Average
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
6
Top 10%
Average
Average
Green
hybrid