The E2F family of
transcription factors plays a pivotal role in the regulation of cellular proliferation. On the basis of sequence homology and function, eight distinct members of
E2F transcription factors (E2F-1 to E2F-8) have been distinguished to date. The regulation of
E2F transcription factors is closely associated with the function of the
retinoblastoma family of
tumor suppressors (RB pathway). In the last decade various alterations of distinct components of the RB-E2F pathway were found to be associated with
tumor progression. However, no data on the role of E2F family members are available in
tumor biology of
ovarian cancer. Here we describe an expression study of
E2F transcription factors in various human
ovarian cancer cell lines; its clinical relevance was examined in a training set of 77
ovarian cancer patients. Expression levels of E2F-1, E2F-2, and E2F-8 were elevated in all the
ovarian cancer cell lines studied when compared with human peritoneal mesothelial cells (HPMCs). Interestingly,
EGF treatment showed a time-dependent upregulation of the activating
transcription factor E2F-3 and a simultaneous increase of DP-1, the heterodimeric partner of E2F-3. High expression of E2F-1, E2F-2, and E2F-8 was found to be associated with histopathologic grade 3
tumors and
residual tumor over 2 cm in diameter after primary debulking surgery in
ovarian cancer patients. Taken together, these data suggest that the proliferation-promoting
E2F transcription factors E2F-1 and especially E2F-2 play a pivotal role in
tumor biology of
ovarian cancer and may be candidates for specific therapeutic targets.