Differential gene expression in a murine model of cancer cachexia

• Published in: American journal of physiology: endocrinology and metabolism 2001-08, Vol.281 (2), p.E289-E297
• Main Authors: Monitto, Constance L, Berkowitz, Dan, Lee, Kyoung Min, Pin, Sokhon, Li, Daqing, Breslow, Michael, O'Malley, Bert, Schiller, Martin
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - complications; Adenocarcinoma - genetics; Animals; Blotting, Northern; Cachexia - etiology; Cachexia - genetics; Cathepsin B - biosynthesis; Cathepsin B - genetics; Clone Cells; Colonic Neoplasms - complications; Colonic Neoplasms - genetics; Disease Models, Animal; Endogenous Retroviruses - genetics; Ferritins - biosynthesis; Ferritins - genetics; Gene Expression Profiling; Gene Library; Insulin-Like Growth Factor Binding Protein 4 - biosynthesis; Insulin-Like Growth Factor Binding Protein 4 - genetics; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; RNA, Messenger - biosynthesis; Tumor Cells, Cultured; Up-Regulation
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.2001.281.2.e289

Departments of 1  Anesthesiology and Critical Care Medicine and 2  Pathology, The Johns Hopkins Hospital, Baltimore, 21287; and 3  Department of Otorhinolaryngology and Head and Neck Surgery, University of Maryland Medical Center, Baltimore, Maryland 21201 Murine adenocarcinoma 16 (MAC16) tumors and cell lines induce cachexia in NMRI nude mice, whereas histologically similar MAC13 tumors do not. After confirming these findings in BALB/c nude mice, we demonstrated that this tissue wasting was not related to decreased food intake or increased total body oxidative metabolism. Previous studies have suggested that MAC16's cachexigenic properties may involve the production of tumor-specific factors. We therefore screened for genes having increased expression in the MAC16 compared with the MAC13 cell line by performing hybridization to a murine cDNA expression array, by generation and comparison of cDNA libraries from each cell line, and by PCR-based subtractive hybridization. Northern blot hybridization was performed to confirm differences in transcript expression. Transcripts encoding insulin-like growth factor binding protein-4, cathepsin B, ferritin light and heavy chain, endogenous long-terminal repeat sequences, and a viral envelope glycoprotein demonstrated increased expression in the MAC16 cell line. The roles of a number of these genes in known metabolic pathways identify them as potential participants in the induction of cachexia. murine adenocarcinoma 13 and 16 cells; cDNA expression array