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  1. Artikel ; Online: Correction: Mcl-1 confers protection of Her2-positive breast cancer cells to hypoxia: therapeutic implications.

    Bashari, Muhammad Hasan / Fan, Fengjuan / Vallet, Sonia / Sattler, Martin / Arn, Melissa / Luckner-Minden, Claudia / Schulze-Bergkamen, Henning / Zörnig, Inka / Marme, Frederik / Schneeweiss, Andreas / Cardone, Michael H / Opferman, Joseph T / Jäger, Dirk / Podar, Klaus

    Breast cancer research : BCR

    2024  Band 26, Heft 1, Seite(n) 58

    Sprache Englisch
    Erscheinungsdatum 2024-04-02
    Erscheinungsland England
    Dokumenttyp Published Erratum
    ZDB-ID 2015059-3
    ISSN 1465-542X ; 1465-5411
    ISSN (online) 1465-542X
    ISSN 1465-5411
    DOI 10.1186/s13058-024-01811-y
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Mcl-1 confers protection of Her2-positive breast cancer cells to hypoxia: therapeutic implications.

    Bashari, Muhammad Hasan / Fan, Fengjuan / Vallet, Sonia / Sattler, Martin / Arn, Melissa / Luckner-Minden, Claudia / Schulze-Bergkamen, Henning / Zörnig, Inka / Marme, Frederik / Schneeweiss, Andreas / Cardone, Michael H / Opferman, Joseph T / Jäger, Dirk / Podar, Klaus

    Breast cancer research : BCR

    2016  Band 18, Heft 1, Seite(n) 26

    Abstract: Background: Molecular mechanisms leading to the adaptation of breast cancer (BC) cells to hypoxia are largely unknown. The anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) is frequently amplified in BC; and elevated Mcl-1 levels have ... ...

    Abstract Background: Molecular mechanisms leading to the adaptation of breast cancer (BC) cells to hypoxia are largely unknown. The anti-apoptotic Bcl-2 family member myeloid cell leukemia-1 (Mcl-1) is frequently amplified in BC; and elevated Mcl-1 levels have been correlated with poor prognosis. Here we investigated the pathophysiologic role of Mcl-1 in Her2-positive BC cells under hypoxic conditions.
    Methods: RNA interference and a novel small molecule inhibitor, EU-5346, were used to examine the role of Mcl-1 in Her2-positive BC cell lines and primary BC cells (sensitive or intrinsically resistant to Her2 inhibitors) under hypoxic conditions (using a hypoxic incubation chamber). Mechanisms-of-action were investigated by RT-PCR, mitochondrial isolation, as well as immunoprecipitation/blotting analysis, and microscopy. The specificity against Mcl-1 of the novel small molecule inhibitor EU5346 was verified in Mcl-1(Δ/null) versus Mcl-1(wt/wt) Murine Embryonic Fibroblasts (MEFs). Proliferation, survival, and spheroid formation were assessed in response to Mcl-1 and Her2 inhibition.
    Results: We demonstrate for a strong correlation between high Mcl-1 protein levels and hypoxia, predominantly in Her2-positive BC cells. Surprisingly, genetic depletion of Mcl-1 decreased Her2 and Hif-1α levels followed by inhibition of BC cell survival. In contrast, Mcl-1 protein levels were not downregulated after genetic depletion of Her2 indicating a regulatory role of Mcl-1 upstream of Her2. Indeed, Mcl-1 and Her2 co-localize within the mitochondrial fraction and form a Mcl-1/Her2- protein complex. Similar to genetically targeting Mcl-1 the novel small molecule Mcl-1 inhibitor EU-5346 induced cell death and decreased spheroid formation in Her2-positive BC cells. Of interest, EU-5346 induced ubiquitination of Mcl-1- bound Her2 demonstrating a previously unknown role for Mcl-1 to stabilize Her2 protein levels. Importantly, targeting Mcl-1 was also active in Her2-positive BC cells resistant to Her2 inhibitors, including a brain-primed Her2-positive cell line.
    Conclusion: Our data demonstrate a critical role of Mcl-1 in Her2-positive BC cell survival under hypoxic conditions and provide the preclinical framework for the therapeutic use of novel Mcl-1- targeting agents to improve patient outcome in BC.
    Mesh-Begriff(e) Animals ; Apoptosis/genetics ; Breast Neoplasms/genetics ; Breast Neoplasms/pathology ; Cell Hypoxia/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Myeloid Cell Leukemia Sequence 1 Protein/biosynthesis ; Myeloid Cell Leukemia Sequence 1 Protein/genetics ; RNA Interference ; Receptor, ErbB-2/genetics ; Signal Transduction/genetics
    Chemische Substanzen MCL1 protein, human ; Myeloid Cell Leukemia Sequence 1 Protein ; ERBB2 protein, human (EC 2.7.10.1) ; Receptor, ErbB-2 (EC 2.7.10.1)
    Sprache Englisch
    Erscheinungsdatum 2016-02-26
    Erscheinungsland England
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2015059-3
    ISSN 1465-542X ; 1465-5411
    ISSN (online) 1465-542X
    ISSN 1465-5411
    DOI 10.1186/s13058-016-0686-4
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 5494: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

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