Therapeutic efficacy of E2F1 in pancreatic cancer correlates with TP73 induction.
Pancreatic cancer is particularly resistant to apoptosis by antineoplastic agents, which is partly attributable to the lack of functional p53. Here we show that E2F1 in combination with the most clinically efficient drug, gemcitabine, resulted in a strong induction of apoptosis independent of functional p53, whereas the effect of either therapy alone varied between different cell lines. Intratumoral injection of a helper-dependent adenovirus vector expressing E2F1 plus drug treatment resulted in a significant reduction of tumor volume. The therapeutic effect is directly correlated with the induction of the p53 homologue p73, suggesting that the recently discovered E2F1/p73 pathway plays a critical role in cancer therapy.
Rödicker
F
F
Centre for Cancer Research and Cancer Therapy, Institute of Molecular Biology, University of Essen, Medical School, D-45122 Essen, Germany.
Stiewe
T
T
Zimmermann
S
S
Pützer
B M
BM
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D018797:Cell Cycle Proteins; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C493754:E2f1 protein, mouse; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D014157:Transcription Factors; C000606368:Trp73 protein, mouse; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D003841:Deoxycytidine; D000093542:Gemcitabine