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Kinetics of wound‐induced v‐Ha‐ ras transgene expression and papilloma development in transgenic Tg.AC mice
Author(s) -
Can Ronald E.,
Spalding Judson W.,
Trempus Carol S.,
Szczesniak Carl J.,
Virgil Kelly M.,
Humble Michael C.,
Tennant Raymond W.
Publication year - 1997
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/(sici)1098-2744(199709)20:1<108::aid-mc12>3.0.co;2-5
Subject(s) - transgene , biology , microbiology and biotechnology , genetically modified mouse , transcription (linguistics) , gene expression , in situ hybridization , gene , genetics , linguistics , philosophy
The Tg.AC transgenic mouse, which harbors an activated v‐Ha‐ ras coding region that is fused to an embryonic ζ globin transcriptional control region and a 3′ simian virus 40 polyadenylation sequence, rapidly develops epidermal papillomas in response to topical application of chemical carcinogens or tumor promoters or to full‐thickness wounding of the dorsal skin. In this report, we investigated the localization and temporal induction of v‐Ha‐ ras transgene expression after full‐thickness wounding of Tg.AC mouse skin. Surgically inflicted full‐thickness incisions 3 cm long yielded four to six papillomas per Tg.AC mouse by 5 wk after wounding. Similar wounding of the FVB/N isogenic host strain did not produce tumors, which implicates a causal role for the v‐Ha‐ ras transgene. Reverse transcription–polymerase chain reaction assays detected the v‐Ha‐ ras transgene transcript in total RNA samples isolated from wound‐associated tissue 3 and 4 wk after wounding. Tissues 1–2 wk after wounding and all non‐wound–associated tissues were negative for transgene expression. In situ hybridization experiments using transgene‐specific 35 S‐labeled antisense RNA probes localized transgene expression to the basal epidermal cells in wound‐induced papillomas. Adjacent normal and hyperplastic skin tissues were negative for transgene expression by this assay. This work supports the hypothesis that the wound repair response leads to the transcriptional activation and continued expression of the v‐Ha‐ ras transgene in specific cells in the skin, which alters normal epithelial differentiation and ultimately results in neoplastic growth. Mol. Carcinog. 20:108–114, 1997. © 1997 Wiley‐Liss, Inc. This article is a US Government work and, as such, is in the public domain in the United States of America.