Carcinogenesis, Vol 19, 2095-2099, Copyright © 1998 by Oxford University Press
M Elkin, S Ayesh, T Schneider, N de Groot, A Hochberg and I Ariel
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.
ARTICLES
The dynamics of the imprinted H19 gene expression in the mouse model of bladder carcinoma induced by N-butyl-N-(4-hydroxybutyl)nitrosamine
Department of Biological Chemistry, Institute for Life Sciences, Hebrew University of Jerusalem, Israel.
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