The Tg.AC transgenic mouse, which harbors an activated v-Ha-ras coding region that is fused to an embryonic
zeta 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 35S-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.