Differential gene expression in a murine model of cancer cachexia

Murine adenocarcinoma 16 (MAC16) tumors and cell lines induce cachexia in N MRI nude mice, whereas histologically similar MAC13 tumors do not. After co nfirming these findings in BALB/c nude mice, we demonstrated that this tiss ue wasting was not related to decreased food intake or increased total body oxidative metabolism. Previous studies have suggested that MAC16's cachexi genic properties may involve the production of tumor-specific factors. We t herefore screened for genes having increased expression in the MAC16 compar ed with the MAC13 cell line by performing hybridization to a murine cDNA ex pression array, by generation and comparison of cDNA libraries from each ce ll line, and by PCR-based subtractive hybridization. Northern blot hybridiz ation was performed to confirm differences in transcript expression. Transc ripts encoding insulin-like growth factor binding protein-4, cathepsin B, f erritin light and heavy chain, endogenous long-terminal repeat sequences, a nd a viral envelope glycoprotein demonstrated increased expression in the M AC16 cell line. The roles of a number of these genes in known metabolic pat hways identify them as potential participants in the induction of cachexia.