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Updated: Jun 30, 2026
Evaluating the Effectiveness of Cancer Drug Sensitization In Vitro and In Vivo
Published on: February 6, 2015
Expression of Arl2 is associated with p53 localization and chemosensitivity in a breast cancer cell line
Anne Béghin1, Eva-Laure Matera, Stephanie Brunet-Manquat
1Université de Lyon, F-69008, INSERM U590, Laboratoire de cytologie analytique, Lyon, France. anne.beghin@recherche.univ-lyon1.fr
Abstract:
In mammalian cells, ADP ribosylation factor like 2 (Arl2) has been shown to form a complex with tubulin binding cofactor D (TBC-D) and the tumor suppressor protein phosphatase 2A (PP2A). We have previously shown that alterations in Arl2 protein content were associated with corresponding modifications of the tumor suppressor PP2Ac protein content in breast cancer cells. Here, we show that modified Arl2 expression level influences sensitivity to various anticancer compounds such as taxol, navelbine, gemcitabine and doxorubicin in MCF7 derived cell lines. Modifications of Arl2 expression levels were also associated with an altered phosphorylation status and/or cellular sublocalization of certain PP2A targets such as p53, a key mediator of chemotherapy-induced apoptosis. A decreased level of Arl2 expression was associated with an increase of phospho-ser15-p53, a form which was found to be preferentially bound to microtubules. Assays using okadaic and cantharidic acid, two different PP2A inhibitors, showed an increase in microtubule-bound phospho-p53 and reduced sensitivity to chemotherapy. Our results suggest that Arl2 could, via PP2A, influence p53 phosphorylation status. Certain forms of phosphorylated p53 demonstrating increased binding to microtubules appear to be less prone to nuclear translocation after exposure to chemotherapeutic agents, thereby possibly contributing to reduced chemosensitivity.
Insights
ADP ribosylation factor like 2 (Arl2) influences breast cancer cell sensitivity to chemotherapy by affecting p53 phosphorylation via protein phosphatase 2A (PP2A). Reduced Arl2 levels increase microtubule-bound p53, potentially lowering treatment effectiveness.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- ADP ribosylation factor like 2 (Arl2) interacts with tubulin binding cofactor D (TBC-D) and protein phosphatase 2A (PP2A) in mammalian cells.
- Previous studies linked Arl2 protein levels to tumor suppressor PP2Ac modifications in breast cancer cells.
Purpose of the Study:
- To investigate the role of Arl2 expression levels in breast cancer cell sensitivity to various anticancer agents.
- To explore the relationship between Arl2, PP2A, and the phosphorylation status and localization of p53.
Main Methods:
- Utilized MCF7-derived cell lines with modified Arl2 expression.
- Assessed sensitivity to chemotherapeutic compounds (taxol, navelbine, gemcitabine, doxorubicin).
- Analyzed p53 phosphorylation and subcellular localization using PP2A inhibitors (okadaic acid, cantharidic acid).
Main Results:
- Modified Arl2 expression levels altered sensitivity to multiple anticancer drugs.
- Changes in Arl2 levels correlated with altered phosphorylation and localization of PP2A targets, including p53.
- Decreased Arl2 increased phospho-ser15-p53, which preferentially bound to microtubules, reducing chemosensitivity.
Conclusions:
- Arl2 influences breast cancer cell chemosensitivity, potentially through its regulation of PP2A activity.
- Arl2 may modulate p53 phosphorylation, affecting its microtubule binding and nuclear translocation.
- Microtubule-bound phosphorylated p53 may contribute to reduced sensitivity to chemotherapy.
