Apoptosis induction by E2F-1 via adenoviral-mediated gene transfer results in growth suppression of head and neck squamous cell carcinoma cell lines.

Abstract

E2F-1, a transcription factor by discovery, is thought to play a crucial role in regulating G1/S cell cycle progression. Its activity is modulated by complex formation with the retinoblastoma protein and related proteins. Overexpression of E2F-1 has been shown to induce apoptosis in quiescent fibroblasts. We constructed a recombinant E2F-1 adenovirus to test whether an overexpression of E2F-1 in head and neck squamous cell carcinoma cell lines would also induce apoptosis. Two cell lines, Tu-138 and Tu-167, were chosen for use in this study. Both cell lines harbor p53 mutations but express different levels of the retinoblastoma protein. Upon E2F-1 adenovirus infection, both cell lines expressed elevated levels of E2F-1 protein and then activated a pRb-chloramphenicol acetyltransferase reporter construct containing an E2F-1 binding motif. In vitro growth assay demonstrated that growth suppression by the E2F-1 protein was effective on both cell lines. Results from DNA fragmentation and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end-labeling analyses indicated apoptosis induction in cells infected with AdCMV-E2F-1. Moreover, ex vivo experiments in nude mice showed total suppression of tumor growth at sites that received cells infected AdCMV-E2F-1. An in vivo analysis of apoptosis using in situ end-labeling further demonstrated the induction of apoptosis by AdCMV-E2F-1 in tumor-bearing animals. These data indicate that overexpression of E2F-1 via an adenoviral vector suppresses in vitro and in vivo growth of head and neck squamous carcinoma cell lines through induction of apoptosis.

• Authors: T J Liu, M Wang, R L Breau, Y Henderson, A K El-Naggar, K D Steck, M W Sicard, G L Clayman
• Journal: Cancer gene therapy (Cancer Gene Ther) 1999 Mar-Apr Vol. 6 Issue 2 Pg. 163-71 ISSN: 0929-1903 [Print] England
• PMID: 10195883 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Arid4a protein, mouse
• Carrier Proteins
• Cell Cycle Proteins
• DNA-Binding Proteins
• E2F Transcription Factors
• E2F1 Transcription Factor
• E2F1 protein, human
• E2f1 protein, mouse
• Retinoblastoma-Binding Protein 1
• Transcription Factor DP1
• Transcription Factors
• Chloramphenicol O-Acetyltransferase

Topics

• Adenoviridae (genetics)
• Animals
• Apoptosis
• Blotting, Western
• Carcinoma, Squamous Cell (therapy)
• Carrier Proteins
• Cell Cycle
• Cell Cycle Proteins
• Cell Division (drug effects)
• Chloramphenicol O-Acetyltransferase (metabolism)
• DNA Fragmentation
• DNA-Binding Proteins
• E2F Transcription Factors
• E2F1 Transcription Factor
• Head and Neck Neoplasms (therapy)
• Humans
• In Situ Nick-End Labeling
• Mice
• Mice, Nude
• Neoplasms, Experimental (pathology)
• Retinoblastoma-Binding Protein 1
• Time Factors
• Transcription Factor DP1
• Transcription Factors (genetics, pharmacology)
• Tumor Cells, Cultured