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Mol Cell Biol. 1989 March; 9(3): 925-934

Cell-heritable stages of tumor progression in transgenic mice harboring the bovine papillomavirus type 1 genome.

M Sippola-Thiele, D Hanahan and P M Howley

Laboratory of Tumor Virus Biology, National Cancer Institute, Bethesda, Maryland 20892.

ABSTRACT

Tumorigenesis of dermal fibroblasts in a line of transgenic mice carrying the BPV-1 genome was found to involve distinct proliferative stages. Cell cultures derived from normal skin, from benign proliferative fibromatoses, and from malignant fibrosarcomas each evidenced distinguishable, cell-heritable characteristics. The latent viral genome was transcriptionally inactive in normal-appearing skin and was activated in the dermal fibromatoses. Fibrosarcoma cells grew continuously in culture, formed domelike foci, and had a more rounded, anaplastic appearance. Independent cultures derived from the fibromatoses varied in their proliferative characteristics, which correlated well with the levels of viral gene expression. In contrast, progression to malignancy was not accompanied by a further increase in transgene activity, which strongly implicated cellular genetic changes in the later stages of tumorigenesis.

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Mol Cell Biol. 1989 March; 9(3): 925-934

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