The imprinted H19 gene product is an oncofetal RNA molecule in humans. It is 
expressed in fetal bladder, down-regulated postnatally and is re-expressed in 
human bladder carcinoma. This study was designed to investigate the dynamics of 
the expression of H19 in the mouse bladder carcinoma induced by 
N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and its relation to stages of 
neoplastic transformation. BBN was administered to mice in the drinking water 
for 26-28 weeks. The bladders were removed at 5-10 week intervals for 
histopathological examination and for in situ hybridization for H19 RNA, using a 
35S-labeled probe. Following BBN administration expression of H19 first appeared 
after 5 weeks in the lamina propria adjacent to the basement membrane, 
concomitant with mucosal hyperplasia. At 11 weeks focal expression was noted in 
epithelial cells. Invasive carcinomas, of the transitional and squamous 
sub-types, were seen after 20 weeks and more of BBN administration. At this 
stage H19 expression was observed in scattered tumor cells, in the connective 
tissue stroma of the tumor and in the lamina propria underlying the remaining 
hyperplastic/dysplastic mucosa. Abundant expression of H19 was evident in fetal 
bladder but was absent in normal adult bladder. We conclude that, similar to 
humans, the H19 gene product is an oncofetal RNA molecule in the experimental 
mouse model of bladder carcinoma. In this model H19 is expressed in the 
connective tissue of the lamina propria prior to its expression in epithelial 
cells, concurrent with preneoplastic changes in the transitional epithelium of 
the bladder.