Immunohistochemical detection of ras and myc oncogene expression in regenerating rat liver

The expression of ras and myc oncogene proteins was examined in formalin-fixed paraffin-embedded sections of male Sprague-Dawley rat liver at various times after liver regeneration was induced by either a necrogenic dose of CCl4 or a 2/3 partial hepatectomy. Antibody specific for these proteins and immunohistochemical (IHC) procedures were used to detect oncogene expression in the liver. Increased expression of both oncogene proteins was detected at times comparable to those reported by others using either Northern or Western blot methods. However, the IHC procedure provided additional information since oncogene expression was detected only in hepatocytes, mainly occupying liver lobule zones known to contain proliferating hepatocytes during regeneration. Also, ras and myc stain intensity of individual hepatocytes did not increase during regeneration. Rather, a greater number of hepatocytes were positive at several time points in the regeneration process. This suggested that the increased ras and myc expression detected in Northern and Western blot methods probably represents a greater number of hepatocytes expressing the oncogene proteins rather than increased expression by individual hepatocytes. Overall, this study provides additional information on the cells involved in the expression of the ras and myc oncogenes during regeneration and further substantiates their role in a normal physiological process.