Unknown,Transcriptomics,Genomics,Proteomics

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Expression data from the bladders of carcinogen-treated mice with genetic Hh pathway manipulation

ABSTRACT: Attenuation of Hedgehog (Hh) pathway activity leads to accelerated tumor progression in a mouse model of N-butyl-N-4-hydroxybutyl nitrosamine (BBN) – induced bladder carcinoma. In order to identify genes regulated by the Hh pathway that might be involved in bladder cancer progression, we performed transcriptional profiling of bladders harvested from mice after BBN-exposure, comparing Gli1CreER/WT; Smoflox/WT mice to Gli1CreER/WT; Smoflox/flox mice, which express CreER under control of the Gli1 promoter and carry one or two floxed alleles of the essential Hh pathway transductory component Smoothened (Smo) respectively. Administration of Tamoxifen to these mice results in attenuation of Hh pathway activty to a greater extent in the Gli1CreER/WT;Smoflox/flox mice as compared to Gli1CreER/WT;Smoflox/WT mice, allowing identification of Hh-pathway regulated genes. 6 total samples were analyzed. 3 bladders from Gli1CreER/WT; Smoflox/WT mice and 3 bladders from Gli1CreER/WT; Smoflox/flox mice were analyzed.

ORGANISM(S): Mus musculus

SUBMITTER: Agnes Lim

PROVIDER: E-GEOD-60654 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Recent studies in our lab have identified a mutant mouse model of obstructive nephropathy designated mgb for megabladder. Homozygotic mgb mice (mgb-/-) develop lower urinary tract obstruction in utero due to a lack of bladder smooth muscle differentiation. This defect is the result of a random transgene insertion into chromosome 16 followed by a translocation of this fragment into chromosome 11. In an effort to identify potential gene targets affected in mgb mice, we performed transcriptional profiling on embryonic day 15 (E15) mgb-/- bladders using both a Chromosome 11/16 Custom GeneChip Array and the Affymetrix Mouse Genome 430 2.0 GeneChip. This analysis identified no definitive mis-expressed gene targets on chromosome 11. In contrast, mgb-/- mice significantly over-expressed a cluster of gene products located on the translocated fragment of chromosome 16 including urotensin II-related peptide (Urp), which was shown to be preferentially over-expressed in developing mgb-/- bladders. Immunohistochemical studies indicated that the spatial distribution of Urp was altered in mgb-/- bladders, while biochemical studies suggested a potential role for Urp in modifying smooth muscle cell phenotype in vitro. Pathway analysis of mgb microarray data showed dysregulation of at least 60 gene products associated with the differentiation of smooth muscle. In conclusion, the results of this study indicate that the molecular pathways controlling normal smooth muscle development are severely altered in mgb-/- bladders, and provide the first evidence that Urp may play a critical role in bladder smooth muscle development. Keywords: mgb mutant bladders Gene expression profiling was performed on two separate study groups. First, total cellular RNA was isolated from wildtype (n=2; 1 female/1 male), mgb+/- (n=2; 1 female/1 male), and mgb-/- (n=2; 1 female/1 male) E15 whole embryos. Second, total cellular RNA was isolated from the bladders of E15 wildtype (n=7; 3 female/4 male), mgb+/- mice (n=7; 3 female/4 male), and mgb-/- mice (n=11; 7 females/4 males).

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Expression data from the bladders of carcinogen-treated mice with genetic Hh pathway manipulation

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