Mammary gland tumor in transgenic mice expressing targeted beta-casein/HPV16E6 fusion gene

The human papillomaviruses (I-IPV)-16 and HPV-18 referred to as high-risk H PVs are strongly associated with anogenital malignancies as well as benign epithelial cysts. It has been demonstrated that transgenic mice carrying HP V-16 E6-E7 under the control of the MMTV LTR developed malignant tumors inc luding salivary gland carcinoma, lymphoma, skin histiocytomas and testicula r tumors in a nonmammary gland specific manner. Another regulatory unit of rat B-casein gene can confer the expression of fusion gene preferently in t he mammary glands of transgenic mice in a developmentally regulated manner. In order to generate mammary tumor formation in transgenic mice directing HPV16E6 gene alone into the mammary gland, this regulatory unit was fused t o the EG gene of HPV-16 type to constructing fusion gene. By screening 51 n ewborn founder transgenic mice, thief mice carrying transgenes were identif ied. One line tel-med TG32 developed in a mammary gland tumor with large su bcutaneous mass in the left rib region at 17 months of age. The levels of E G transcript in the mass-tumor of TG32 line were lower than those in non-tu mor mammary gland of identical TG32 and of TG250. In each tissue of TG32 li ne, high expression of EG transcript was detected both in the mammary gland and blain. Histological analysis showed that cells from mammary gland turn er of the TG32 line had also hyperplasia appearance, with irregular or incr eased total number of mitotic rate. These observations suggest that develop ing phenotype and the level of Eb transcripts in the process of malignant t ransformation may have different mechanisms involving the capacity to bind and destabilize p53, although for confirmation it is necessary to investiga te many more transgenic mice.