B72
Effects of ∆133 isoform of p53 on the growth and metastasis ability of the breast cancer cell MCF7 in xenograft models
Karen Murray, Virginia Appleyard, Jean-Christophe Bourdon, Alastair Thompson
Centre for Oncology and Molecular Medicine, University of Dundee, UK
Background.
Studies in several tumour types have shown that the nine different p53 isoforms are abnormally expressed in tumour tissues compared to normal cells. This study examines the effects of ∆133 isoform of p53 on the growth and metastasis ability of the breast cancer cell MCF7 in xenograft models.
Method
Model 1: Female nude mice implanted with oestrogen pellets were subcutaneously injected with MCF7 cells bearing a ∆133 isoform of p53 or MCF7 containing an empty vector. Tumours were measured twice a week for 50 days.
Model 2: Female nude mice implanted with oestrogen pellets were orthotopically injected with MCF7 bearing a ∆133 isoform of p53 or MCF7 containing an empty vector. After 30 days, mice that developed tumours were sacrificed and lungs harvested in RNA later for further PCR analysis to determine metastasis.
Results
Model 1: 8 out of 25 mice subcutaneously injected with wt p53 MCF7 cells developed tumours (32%), with a final average size of 236 mm3 whereas 12 out of 24 mice subcutaneously injected with ∆133 p53 - MCF7 developed tumours (48%), with a final average size of 344 mm3.
Model 2: 8 out of 10 mice orthotopically injected with wt p53 MCF7 developed tumours (80%). From these, 2 were metastatic (25%). 5 out of 10 mice orthotopically injected with ∆133 p53 isoform MCF7 developed tumours (50 %). From these, 3 were metastatic (60%).
Conclusion
The ∆133 isoform of p53 influences the establishment and metastatic ability of tumours in MCF7 breast cancer xenografts. The ∆133 isoform bearing MCF7 resulted in a higher proportion of faster growing xenograft tumours than unmodified MCF7. Although the tumourigenicity of the ∆133 cell line was not increased by orthotopic injection, it did show an enhanced metastatic ability compared with the unmodified MCF7.
