Sasagawa T, Kondoh G, Inoue M, Yutsudo M, Hakura A
Department of Tumor Virology, Osaka University, Japan.
J Gen Virol. 1994 Nov;75 ( Pt 11):3057-65. doi: 10.1099/0022-1317-75-11-3057.
Half of the female transgenic mice harbouring human papillomavirus type 16 (HPV-16) E6-E7 genes under control of the mouse mammary tumour virus promoter, developed malignant tumours, including salivary gland carcinomas, lymphomas and skin histiocytomas. Although the E6-E7 genes are aetiological factors for human anogenital carcinoma, the transgenic mice produced no tumours in the anogenital tract. We investigated cytological and histological changes in the anogenital tract of the same transgenic mice. Seventeen (77%) of 22 transgenic mice developed dysplastic and/or hyperplastic changes in the cervix and vagina. HPV-16 E6-E7 mRNA signals were observed in the genital lesions, while they were not detected in the normal cervices and vaginas of transgenic mice and control mice by RNA in situ hybridization analysis. RNA/PCR analysis using poly(A)+ RNA showed that only a full-length E6-E7 RNA was expressed in three scraped cell samples from dysplasia, whereas full-length and spliced E6-E7 transcripts were in three cell samples from dysplasia/hyperplasia. These results suggest that expression of both E6 and E7 genes of HPV-16 is important for inducing dysplastic and hyperplastic changes in the genital epithelium.
在小鼠乳腺肿瘤病毒启动子控制下携带人乳头瘤病毒16型（HPV-16）E6-E7基因的雌性转基因小鼠中，有一半发生了恶性肿瘤，包括唾液腺癌、淋巴瘤和皮肤组织细胞瘤。尽管E6-E7基因是人类肛门生殖器癌的病因，但转基因小鼠在肛门生殖道未产生肿瘤。我们研究了同一转基因小鼠肛门生殖道的细胞学和组织学变化。22只转基因小鼠中有17只（77%）在子宫颈和阴道出现发育异常和/或增生性变化。通过RNA原位杂交分析，在生殖器病变中观察到HPV-16 E6-E7 mRNA信号，而在转基因小鼠和对照小鼠的正常子宫颈和阴道中未检测到。使用聚腺苷酸加尾RNA进行的RNA/PCR分析表明，在来自发育异常的三个刮取细胞样本中仅表达全长E6-E7 RNA，而在来自发育异常/增生的三个细胞样本中存在全长和剪接的E6-E7转录本。这些结果表明，HPV-16的E6和E7基因的表达对于诱导生殖器上皮的发育异常和增生性变化很重要。
