The Tg.AC transgenic @entity19 carries a v-Ha-ras transgene. @entity272 develop in Tg.AC @entity19 upon repeated dermal application of @entity5 promoters and carcinogens. The transgene is inserted at a single site on chromosome 11 in a multiple-copy array. Although most of the >or= 40 copies are arranged in a direct-repeat orientation, two copies of the transgene are inserted in a palindromic, inverted-repeat orientation. Deletion of the palindromic transgene promoter sequence is associated strongly with and diagnostic of loss of phenotypic responsiveness to Tg.AC papillomagens, such as @entity864 ( @entity865 ). Unexpectedly, a loss of palindromic transgene sequence, in the absence of an observable reduction in copy number of the direct-repeat-oriented transgene sequence, is seen in DNA from @entity1185 when compared to genomic DNA from tail clips or skin samples away from the application site. Transgene-derived transcripts were detectable in all Tg.AC @entity1185 sampled. The transgene locus was hypomethylated in @entity1185 but not in samples from tail clips from the same animal or from skin samples away from the application site in responder Tg.AC @entity19 , as shown by loss of resistance to digestion by HpaII. A cell line derived from a Tg.AC @entity957 showed complete loss of the palindromic transgene sequence, hypomethylation of the transgene locus, and strong expression of v-Ha-ras mRNA. These data indicate that the palindromic transgene sequence, which appears to be necessary for initial responsiveness to tumorigens, may be susceptible to deletion during rapid cellular proliferation and is not required for transgene expression in later phases of @entity1185 growth.

Loss of critical palindromic transgene promoter sequence in chemically induced Tg.AC @entity19 XXXX expressing transgene-derived mRNA.

@entity19 :: ('10090', 'Species') :: ['mice', 'mouse'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity1185 :: ('MESH:D010212', 'Disease') :: ['papillomas', 'papilloma'] @entity957 :: ('MESH:D002294', 'Disease') :: ['squamous cell carcinoma'] @entity865 :: ('CHEBI:61432', 'Chemical') :: ['TPA'] @entity272 :: ('MESH:D012871', 'Disease') :: ['Skin papillomas'] @entity864 :: ('MESH:C554292|MESH:D013755', 'Chemical') :: ['12-O-tetradecanoylphorbol-13-acetate']
@entity272 :: (MESH:D012871,Disease) :: ['skin papillomas']
