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Transactivation-deficient DeltaTA-p73 acts as an oncogene
Thorsten Stiewe1, Sonja Zimmermann, Andreja Frilling
1Centre for Cancer Research and Cancer Therapy, Institute of Molecular Biology, University of Essen, Medical School, D-45122 Essen, Germany.
Cancer Research
|July 5, 2002
Summary
Truncated p73 proteins (DeltaTA-p73), lacking transactivation function, are overexpressed in human cancers. DeltaTA-p73 promotes malignant transformation and tumor growth, indicating an oncogenic role for the TP73 gene in cancer development.
Area of Science:
- Molecular Biology
- Oncology
- Genetics
Background:
- The p53-family member p73 shares homology with p53.
- Evidence suggests p73 may not function as a classical tumor suppressor.
- The role of truncated p73 isoforms in cancer is largely unexplored.
Purpose of the Study:
- To investigate the function of NH(2)-terminally truncated, transactivation-deficient p73 proteins (DeltaTA-p73).
- To determine if DeltaTA-p73 overexpression contributes to cancer development.
- To provide experimental evidence for the oncogenic potential of DeltaTA-p73.
Main Methods:
- Analysis of DeltaTA-p73 expression in human cancer cells.
- Malignant transformation assays using NIH3T3 fibroblasts.
- Tumorigenicity studies in nude mice.
Main Results:
- Overexpression of DeltaTA-p73 was observed in human cancer cells.
- DeltaTA-p73 overexpression induced malignant transformation of fibroblasts.
- DeltaTA-p73 promoted tumor growth in vivo.
Conclusions:
- The TP73 gene can acquire oncogenic activity through increased expression of truncated isoforms.
- DeltaTA-p73 possesses oncogenic functions, contributing to tumor development.
- The findings suggest that DeltaTA-p73 is actively selected for during tumorigenesis.