Transcription factors junB and c-jun are selectively up-regulated and functionally implicated in fibrosarcoma development.

Abstract

Bovine papillomavirus transgenic mice develop skin tumors arising from dermal fibroblasts in a process comprised of three distinctive stages: mild and aggressive fibromatoses, and fibrosarcoma. In both tissue biopsies and derivative cell lines, the proto-oncogenes junB and c-jun are induced in the latter two stages, in contrast to junD and fos. Fibrosarcoma cell lines have increased AP-1 DNA-binding activity. Overexpression of junB or c-jun by transfection into the mild fibromatosis stage elicited changes in cell shape and anchorage independence, whereas junD did not. Similar transfections of normal skin fibroblasts had no effect. Thus, junB and c-jun represent progression factors whose activities are necessary at an intermediate stage of tumor development, subsequent to the initiation of aberrant proliferation.