Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing
| Autor: | Jacques Beau, Sandrine Dulong, Yoshiro Fujii, Michèle Teboul, Franck Delaunay, Bruno Claustrat, Sinisa Zampera, Francis Lévi, Xiao-Mei Li |
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| Přispěvatelé: | Laboratoire de physiologie des membranes cellulaires (LPMC), Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Rythmes Biologiques et Cancers, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'anatomie pathologique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Unité de chronothérapie |
| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Male
Cancer Research MESH: Body Temperature Circadian clock Endogeny CIRBP Body Temperature Transcriptome Mice 0302 clinical medicine Neoplasms MESH: Reverse Transcriptase Polymerase Chain Reaction MESH: Animals MESH: Neoplasms MESH: Animal Feed [SDV.BDD]Life Sciences [q-bio]/Development Biology Oligonucleotide Array Sequence Analysis 2. Zero hunger 0303 health sciences Reverse Transcriptase Polymerase Chain Reaction MESH: Gene Expression Regulation Neoplastic Circadian Rhythm PER2 CLOCK Gene Expression Regulation Neoplastic Oncology Liver 030220 oncology & carcinogenesis Disease Progression MESH: Disease Progression MESH: Pancreatic Neoplasms medicine.medical_specialty Biology 03 medical and health sciences MESH: Gene Expression Profiling Internal medicine medicine Zeitgeber Animals Circadian rhythm MESH: Circadian Rhythm MESH: Mice 030304 developmental biology Gene Expression Profiling Body Weight Animal Feed MESH: Male MESH: Body Weight Pancreatic Neoplasms Endocrinology MESH: Oligonucleotide Array Sequence Analysis MESH: Liver |
| Zdroj: | Cancer Research Cancer Research, American Association for Cancer Research, 2010, 70 (8), pp.3351-60. ⟨10.1158/0008-5472.CAN-09-4235⟩ |
| ISSN: | 0008-5472 1538-7445 |
| DOI: | 10.1158/0008-5472.CAN-09-4235⟩ |
| Popis: | Circadian disruption accelerates cancer progression, whereas circadian reinforcement could halt it. Mice with P03 pancreatic adenocarcinoma (n = 77) were synchronized and fed ad libitum (AL) or with meal timing (MT) from Zeitgeber time (ZT) 2 to ZT6 with normal or fat diet. Tumor gene expression profiling was determined with DNA microarrays at endogenous circadian time (CT) 4 and CT16. Circadian mRNA expression patterns were determined for clock genes Rev-erbα, Per2, and Bmal1, cellular stress genes Hspa8 and Cirbp, and cyclin A2 gene Ccna2 in liver and tumor. The 24-hour patterns in telemetered rest-activity and body temperature and plasma corticosterone and insulin-like growth factor-I (IGF-I) were assessed. We showed that MT inhibited cancer growth by ∼40% as compared with AL (P = 0.011) irrespective of calorie intake. Clock gene transcription remained arrhythmic in tumors irrespective of feeding schedule or diet. Yet, MT upregulated or downregulated the expression of 423 tumor genes, according to CT. Moreover, 36 genes involved in cellular stress, cell cycle, and metabolism were upregulated at one CT and downregulated 12 h apart. MT induced >10-fold circadian expression of Hspa8, Cirbp, and Ccna2 in tumors. Corticosterone or IGF-I patterns played no role in tumor growth inhibition. In contrast, MT consistently doubled the circadian amplitude of body temperature. Peak and trough respectively corresponded to peak expressions of Hspa8 and Cirbp in tumors. The reinforcement of the host circadian timing system with MT induced 24-hour rhythmic expression of critical genes in clock-deficient tumors, which translated into cancer growth inhibition. Targeting circadian clocks represents a novel potential challenge for cancer therapeutics. Cancer Res; 70(8); 3351–60. ©2010 AACR. |
| Databáze: | OpenAIRE |
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