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KMID : 0604220050120030055
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Korean Journal Investigative Dermatology
2005 Volume.12 No. 3 p.55 ~ p.59
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Increased Susceptibility to Actinic Keratosis in HPV18 E6/E7 Transgenic Mice
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Ha Hye-Yeong
Ryoo Zae-Young
Hwang Ha-Young
Kim Tae-Yoon
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Abstract
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The E6 and E7 early genes of human papillomavirus type 18(HPV18) has been known to play role in human cancer due to transforming properties. Our previous study have showed that the transgenic mice in which expression of HPV 18 E6/E7 is under the control of the promoter present in its own upstream regulatory region(URR)(Tg HPV18 URR E6/E7) exhibited dramatic expression of the transgene in skin and cervix. In this study, to examine the functional roles of E6 and E7 gene in skin, we investigated the expression of E6/E7 transcripts of splicing variants in the Tg HPV18 URR E6/E7 by RT-PCR analysis. The results indicated that strong expression of E6*-E7 splicing transcript compare to the E6/E7 full length transcript in the skin of Tg HPV18 URR E6/E7. The predominant transcript of E6*-E7 has been suggested that specifically induces hyperproliferation of keratinocyte. In addition, we analyzed the skin of Tg HPV18 URR E6/E7 by conducting two-step carcinogenesis experiment using 7, 12-dimethylbenzanthracene(DMBA) and 12-O-tetradecanoylphorbol-13-acetate(TPA). Although gross visual examination failed to detect any papillomas in the transgenic mice after 15 weeks of DMBA/TPA treatment, histological staining of the skin revealed the indication of morphological alteration, is known as epidermal hyperplasia or actinic keratosis in Tg HPV18 URR E6/E7(n=6). This alteration was not detected, however, in DMBA/TPA treated wild-type littermates or acetone-treated transgenic littermates(n=5). Even though the transgenic mice were previously reported in which E6/E7 is expressed from strong heterologous promoters including keratin 1, keratin14 and involucrin, this is the first case of showing expression of HPV E6/E7 from its generic promoter in skin. Therefore, our results suggest possible application of the HPV18 URR E6/E7 transgenic mouse to study induction and progression of HPV dependent skin diseases.
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KEYWORD
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Transgenic mouse, Human papillomavirus type 18 E6/E7, Two-step carcinogenesis, Actinic keratosis
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