Loss of USF transcriptional activity in breast cancer cell lines

USF is a family of transcription factors that are structurally related to t he Myc oncoproteins and also share with Myc a common DNA-binding specificit y. USF overexpression can prevent c-Myc-dependent cellular transformation a nd also inhibit the proliferation of certain transformed cells, These antip roliferative activities suggest that USF inactivation could be implicated i n carcinogenesis. To explore this possibility, we compared the activities o f the ubiquitous USF1 and USF2 proteins in several cell lines derived from either normal breast epithelium or breast tumors. The DNA-binding activitie s of USF1 and USF2 were present at similar levels in all cell lines. In the non-tumorigenic MCF-10A cells, USF in general, and USF2 in particular, exh ibited strong transcriptional activities. In contrast, USF1 and USF2 were c ompletely inactive in three out of six transformed breast cell lines invest igated, while the other three transformed cell lines exhibited loss of USF2 activity. Analyses in cells cultured from healthy tissue confirmed the tra nscriptional activity of USF in normal human mammary epithelial cells. Thes e results demonstrate that a partial or complete loss of USF function is a common event in breast cancer cell lines, perhaps because, like Myc overexp ression, it favors rapid proliferation.