Research article summary (published 29 Sep 2009):

Amphiregulin is a factor for resistance of glioma cells to cannabinoid-induced apoptosis.

Full Abstract

Gliomas, one of the most malignant forms of cancer, exhibit high resistance to conventional therapies. Identification of the molecular mechanisms responsible for this resistance is therefore of great interest to improve the efficacy of the treatments against these tumors. Delta9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the ability of these compounds to induce apoptosis of tumor cells. By analyzing the gene expression profile of two sub-clones of C6 glioma cells with different sensitivity to cannabinoid-induced apoptosis, we found a subset of genes with a marked differential expression in the two sub-clones. Furthermore, we identified the epidermal growth factor receptor ligand amphiregulin as a candidate factor to mediate the resistance of glioma cells to cannabinoid treatment. Amphiregulin was highly overexpressed in the cannabinoid-resistant cell line, both in culture and in tumor xenografts. Moreover, in vivo silencing of amphiregulin rendered the resistant tumors xenografts sensitive to cannabinoid antitumoral action. Amphiregulin expression was associated with increased extracellular signal-regulated kinase (ERK) activation, which mediated the resistance to THC by blunting the expression of p8 and TRB3-two genes involved in cannabinoid-induced apoptosis of glioma cells. Our findings therefore identify Amphirregulin as a factor for resistance of glioma cells to THC-induced apoptosis and contribute to unraveling the molecular bases underlying the emerging notion that targeted inhibition of the EGFR pathway can improve the efficacy of antitumoral therapies. (c) 2009 Wiley-Liss, Inc.

Author information

Author/s: Lorente, Mar (M); Carracedo, Arkaitz (A); Torres, Sofía (S); Natali, Francesco (F); Egia, Ainara (A); Hernández-Tiedra, Sonia (S); Salazar, María (M); Blázquez, Cristina (C); Guzmán, Manuel (M); Velasco, Guillermo (G);

Affiliation: Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Glia (Glia), published in United States. (Language: eng)

Reference: 2009-Oct; vol 57 (issue 13) : pp 1374-85

Dates: Created 2009/08/31; Completed 2009/10/30;

PMID: 19229996, status: MEDLINE (last retrieval date: 10/30/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Antineoplastic Agents - pharmacology Apoptosis - drug effects; genetics; physiology Basic Helix-Loop-Helix Transcription Factors - metabolism Cell Cycle Proteins - metabolism Cell Line, Tumor Cell Survival - drug effects; genetics; physiology Drug Resistance, Neoplasm - genetics; physiology Enzyme Activation - genetics; physiology Extracellular Signal-Regulated MAP Kinases - metabolism Gene Expression

Glioma - drug therapy; genetics; pathology; physiopathology Glycoproteins - genetics; metabolism Intercellular Signaling Peptides and Proteins - genetics; metabolism Mice Mice, Nude Neoplasm Proteins - metabolism Neoplasm Transplantation Protein Kinases - metabolism Rats Tetrahydrocannabinol - pharmacology Xenograft Model Antitumor Assays

Associated Chemicals: Antineoplastic Agents (0) ; Basic Helix-Loop-Helix Transcription Factors (0) ; Cell Cycle Proteins (0) ; Glycoproteins (0) ; Intercellular Signaling Peptides and Proteins (0) ; Neoplasm Proteins (0) ; Nupr1 protein, rat (0) ; TRB3 protein, mouse (0) ; amphiregulin (117147-70-3) ; Tetrahydrocannabinol (1972-08-3) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.1.37) ; Protein Kinases (EC 2.7.1.37) ; Trib3 protein, rat (EC 2.7.1.37)

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