Altered glucose metabolism and proteolysis in pancreatic cancer cell conditioned myoblasts: searching for a gene expression pattern with a microarray analysis of 5000 skeletal muscle genes. Issue 8 (9th July 2004)

• Record Type: Journal Article
• Authors: Basso, D; Millino, C; Greco, E; Romualdi, C; Fogar, P; Valerio, A; Bellin, M; Zambon, C-F; Navaglia, F; Dussini, N; Avogaro, A; Pedrazzoli, S; Lanfranchi, G; Plebani, M
• Is Part Of: Gut. Volume 53:Issue 8(2004)
• Page Start: 1159
• Page End: 1166
• Publication Date: 2004-07-09
• Subjects: CM, conditioned media -- DMEM, Dulbecco's modified Eagle's medium -- FCS, fetal calf serum -- PBS, phosphate buffered saline -- NCM, non-conditioned medium -- TC, tumour conditioned -- MW, molecular weight -- RT-PCR, reverse transcription-polymerase chain reaction -- ECHS1, enoyl coenzyme A hydratase -- IGF2R, insulin-like growth factor 2 receptor -- VAMP5, vesicle associated membrane protein 5 -- FLNA, filamin A -- PCCB, propionyl coenzyme A carboxylase -- RPS16, ribosomal protein S16; cachexia -- diabetes mellitus -- micoarray -- myoblasts -- pancreatic cancer; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2003.024471
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background and aims: We verified whether conditioned media (CM) from pancreatic cancer cell lines (MIAPaCa2, CAPAN-1, PANC-1, BxPC3) alter glucose metabolism and gene expression profiles (microarray experiment with a platform of 5000 skeletal muscle cDNA) in mice myoblasts. Methods: Myoblasts were incubated with control or pancreatic cancer CM for 24 and 48 hours. Results: Lactate significantly increased in CM compared with non-conditioned myoblasts. No variations in expression levels of the main genes involved in glycolysis were found in CM myoblasts. Propionyl coenzyme A carboxylase and isocitrate dehydrogenase 3 beta genes, which encode enzymes of the tricarboxylic acid cycle, were overexpressed, while IGFIIR and VAMP5 genes were underexpressed in CM myoblasts. PAFAH1B1 and BCL-2 genes (intracellular signal transduction) and the serine protease cathepsin G (proteolysis), were overexpressed in CM myoblasts. Tyrosine accumulation in CM myoblasts suggested that proteolysis overcomes protein synthesis. Sorcin, actin alpha, troponin T1, and filamin A were underexpressed in CM myoblasts. Conclusions: Our findings demonstrate that pancreatic cancer cell conditioned media enhanced lactate production and induced proteolysis, possibly by altering expression levels of a large number of genes, not only those involved in protein biosynthesis and degradation or glucose metabolism, but also those involved in the tricarboxylic acid cycle and in vesicle traffic.