title: IL-17A and its homologs IL-25/IL-17E recruit the c-RAF/S6 kinase pathway and the generation of pro-oncogenic LMW-E in breast cancer cells.
abstract: Pro-inflammatory IL-17 cytokines were initially described for their pathogenic role in chronic inflammatory diseases and subsequent accumulating evidence indicated their involvement in carcinogenesis. In the present study we report that IL-17A and IL-17E receptors subunits mRNA expressions are upregulated in breast cancers versus normal samples. IL-17E, which is undetectable in most normal breast tissues tested, seems more expressed in some tumors. Investigation of the molecular signaling following stimulation of human breast cancer cell lines with IL-17A and IL-17E showed that both cytokines induced the phosphorylation of c-RAF, ERK1/2 and p70 S6 Kinase were involved in the proliferation and survival of tumor cells. Accordingly, IL-17A and IL-17E promoted resistance to Docetaxel and failed to induce apoptosis as previously reported for IL-17E. Interestingly, we also revealed that both cytokines induced the generation of tumorogenic low molecular weight forms of cyclin E (LMW-E), which high levels correlated strongly with a poor survival in breast cancer patients. These results show for the first time some of the molecular pathways activated by IL-17A and IL-17E that may participate to their pro-oncogenic activity in breast cancers.
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) U976, Hôpital Saint Louis, 75010 Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Immunologie Dermatologie &Oncologie, UMR-S 976, F-75475, Paris, France [3] Institut Jean Godinot, Unicancer, F- 51726 Reims, France [4] Université Reims-Champagne-Ardenne, DERM-I-C, EA7319, 51 rue Cognacq-Jay, 51095 Reims Cedex, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Mombelli
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) U976, Hôpital Saint Louis, 75010 Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Immunologie Dermatologie &Oncologie, UMR-S 976, F-75475, Paris, France [3] OREGA Biotech, F-69130 Ecully, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Cochaud
authors.affiliation: 1] Institut Jean Godinot, Unicancer, F- 51726 Reims, France [2] Université Reims-Champagne-Ardenne, DERM-I-C, EA7319, 51 rue Cognacq-Jay, 51095 Reims Cedex, France.
authors.forename: Yacine
authors.initials: Y
authors.lastname: Merrouche
authors.affiliation: Institut Jean Godinot, Unicancer, F- 51726 Reims, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Garbar
authors.affiliation: Université Reims-Champagne-Ardenne, DERM-I-C, EA7319, 51 rue Cognacq-Jay, 51095 Reims Cedex, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Antonicelli
authors.affiliation: 1] OREGA Biotech, F-69130 Ecully, France [2] IRCM, Institut de Recherche en Cancérologie de Montpellier; INSERM, U896; Université Montpellier 1; CRLC Val d'Aurelle Paul Lamarque, Montpellier, F-34298, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Laprevotte
authors.affiliation: OREGA Biotech, F-69130 Ecully, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Alberici
authors.affiliation: IRCM, Institut de Recherche en Cancérologie de Montpellier; INSERM, U896; Université Montpellier 1; CRLC Val d'Aurelle Paul Lamarque, Montpellier, F-34298, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bonnefoy
authors.affiliation: 1] IRCM, Institut de Recherche en Cancérologie de Montpellier; INSERM, U896; Université Montpellier 1; CRLC Val d'Aurelle Paul Lamarque, Montpellier, F-34298, France [2] Département d'Immunologie, Centre Hospitalier Régional Universitaire de Montpellier et Faculté́ de Médecine Université Montpellier 1, Montpellier, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Eliaou
authors.affiliation: OREGA Biotech, F-69130 Ecully, France.
authors.forename: Jérémy
authors.initials: J
authors.lastname: Bastid
authors.affiliation: 1] Institut National de la Santé et de la Recherche Médicale (INSERM) U976, Hôpital Saint Louis, 75010 Paris, France [2] Université Paris Diderot, Sorbonne Paris Cité, Laboratoire Immunologie Dermatologie &Oncologie, UMR-S 976, F-75475, Paris, France.
authors.forename: Armand
authors.initials: A
authors.lastname: Bensussan
authors.affiliation: 1] Institut Jean Godinot, Unicancer, F- 51726 Reims, France [2] Université Reims-Champagne-Ardenne, DERM-I-C, EA7319, 51 rue Cognacq-Jay, 51095 Reims Cedex, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Giustiniani
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001706:Biopsy; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019927:Cyclin E / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism*; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D000970:Antineoplastic Agents; D019927:Cyclin E; D020381:Interleukin-17; D053722:Receptors, Interleukin-17; D019908:Proto-Oncogene Proteins c-raf; D019893:Ribosomal Protein S6 Kinases