Expression of E2F-1 and E2F-4 is reduced in primary and metastatic breast carcinomas.

The E2F family of transcription factors can induce both cell proliferation and apoptosis. Whether they function as oncogenes or tumor suppressors appears to be tissue specific. Their role in breast carcinogenesis remains unclear. We found a decreased expression of E2F-1 and E2F-4 in 70% (7/10) of primary breast carcinomas and in all (10/10) metastatic nodal tissues when compared with the corresponding normal breast tissue. No tumor-specific mutation was detected, but polymorphisms were identified in E2F-1 exon 5 and in the polyserine tract of E2F-4. The presence of polymorphisms did not correlate with E2F expression. Among the 12 human breast cancer cell lines, one contained a missense mutation in E2F-1 exon 2. Five (42%) cell lines overexpressed E2F-1, while three (25%) expressed low levels of the protein. Our results suggest that not only are the E2Fs likely to function as tumor suppressors in breast cancer, but also that their down-regulation may be important in the development of metastases.