Over-expression of p53 mutants in LNCaP cells alters tumor growth and angiogenesis in vivo
- Oncology Research Centre, Prince of Wales Hospital, Barker St., Randwick, NSW 2031 (Australia)
- Stem Cell Biology Program, Children's Cancer Institute of Australia, NSW (Australia)
- Translational Cancer Research Group, General Hospital Sint-Augustinus and University of Antwerp, Oosterveldlaan 24, B2610 Wilrijk (Belgium)
- Oncology Research Centre, Prince of Wales Hospital, Barker St., Randwick, NSW 2031 (Australia) and Department of Clinical Medicine, University of New South Wales, Kensington, NSW 2052 (Australia)
This study has investigated the impact of three specific dominant-negative p53 mutants (F134L, M237L, and R273H) on tumorigenesis by LNCaP prostate cancer cells. Mutant p53 proteins were associated with an increased subcutaneous 'take rate' in NOD-SCID mice, and increased production of PSA. Tumors expressing F134L and R273H grew slower than controls, and were associated with decreased necrosis and apoptosis, but not hypoxia. Interestingly, hypoxia levels were increased in tumors expressing M237L. There was less proliferation in F134L-bearing tumors compared to control, but this was not statistically significant. Angiogenesis was decreased in tumors expressing F134L and R273H compared with M237L, or controls. Conditioned medium from F134L tumors inhibited growth of normal human umbilical-vein endothelial cells but not telomerase-immortalized bone marrow endothelial cells. F134L tumor supernatants showed lower levels of VEGF and endostatin compared with supernatants from tumors expressing other mutants. Our results support the possibility that decreased angiogenesis might account for reduced growth rate of tumor cells expressing the F134L p53 mutation.
- OSTI ID:
- 20854344
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 345, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2006.05.020; PII: S0006-291X(06)01066-7; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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