Expression of the E2F family of transcription factors and its clinical relevance in ovarian cancer.
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.
Reimer
Daniel
D
Department of Obstetrics and Gynecology, Medical University Innsbruck, Anichstrasse 35, A-6020 Innsbruck. daniel.reimer@uibk.ac.at
Sadr
Susann
S
Wiedemair
Annemarie
A
Goebel
Georg
G
Concin
Nicole
N
Hofstetter
Gerda
G
Marth
Christian
C
Zeimet
Alain G
AG
D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002478:Cells, Cultured; D050684:E2F Transcription Factors / Q000096:biosynthesis* / Q000235:genetics* / Q000502:physiology; D050687:E2F1 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D050703:E2F2 Transcription Factor / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D005810:Multigene Family; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D012097:Repressor Proteins / Q000096:biosynthesis / Q000235:genetics
D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D050703:E2F2 Transcription Factor; C504723:E2F8 protein, human; D012097:Repressor Proteins