Expression of the E2F Family of Transcription Factors and Its Clinical Relevance in Ovarian Cancer

Abstract

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.

Site-specific regulation of cell cycle and DNA repair in post-mitotic GABA cells in schizophrenic versus bipolars

“…The latter include E2F, a positive regulator of transcription (13) and EP300, a histone acetyltransferase that releases promoter activity via chromatin remodeling (14). Another key element is the retinoblastoma protein (Rb), which, by forming a complex with the tyrosine kinase ABL (15), suppresses the transcriptional complex (16).…”

E2F8 Contributes to Human Hepatocellular Carcinoma via Regulating Cell Proliferation

“…The expression levels of E2F1, E2F2, and E2F8 were elevated in the ovarian cancer cells (27). Besides, E2F1 was overexpressed in breast cancers (28), pancreatic ductal carcinoma (29), and gastric cancer (30).…”

Oncogenic Pathway Signatures and Survival Outcome

“…It has been shown that transcription factor E2F1 interacts with the p53 and PI3K pathway. (Hallstrom, Mori, & Nevins, 2008;Reimer et al, 2006; Its role in ovarian cancer has been unclear, as other research groups have found similar favourable survival with increased E2F1 pathway activation (Hallstrom et al, 2008), while other findings have shown favourable survival with decreased E2F1 gene expression by RT-PCR. (Reimer et al, 2006; It must be remarked that the latter study included an overrepresentation of patients with clear cell carcinomas (42.9%) and may be less informative here.…”