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Down-regulation of an abundant cellular protein associated with tumor progression
S Lawson1, D Goldstein, G Latter
1Linus Pauling Institute of Science and Medicine, Palo Alto, CA 94306.
Abstract:
Alteration of gene expression in neoplastic cells can be detected by two-dimensional gel electrophoresis. This study reports the altered synthesis of an abundant cellular protein, p29, accompanying tumorigenic transformation of immortalized fibroblasts induced by transfection with oncogenic DNA. Cell lines derived from morphologically transformed foci synthesized p29 at 60-75% reduced levels compared with untransformed parental cells. Upon inoculation into syngeneic immunocompetent animals, transformed cells gave rise to tumors which were excised and established in culture. The amount of p29 in both focal and tumor-derived lines was inversely correlated with the latent period for tumor formation. In cell lines with a tumor latency of 12-20 days, the level of p29 was decreased by 90-99%. In rapidly tumorigenic cells with a short latency (3-6 days), p29 synthesis was not detectable. These data demonstrate that p29 may be a sensitive and reliable marker for tumor progression of fibroblasts.
Insights
Reduced levels of the abundant cellular protein p29 accompany fibroblast transformation and tumor progression. Lower p29 synthesis correlates with shorter tumor latency, suggesting p29 as a potential marker for neoplastic progression.
Area of Science:
- Molecular Biology
- Cell Biology
- Oncology
Background:
- Neoplastic transformation involves alterations in gene expression.
- Identifying markers for tumor progression is crucial in cancer research.
Purpose of the Study:
- To investigate the role of abundant cellular protein p29 in fibroblast tumorigenic transformation.
- To determine if p29 levels correlate with tumor progression in fibroblasts.
Main Methods:
- Two-dimensional gel electrophoresis to detect protein synthesis alterations.
- Transfection of immortalized fibroblasts with oncogenic DNA.
- Inoculation of transformed cells into animals to assess tumorigenicity and tumor latency.
Main Results:
- Transformed fibroblasts showed 60-75% reduced p29 synthesis compared to parental cells.
- p29 levels were inversely correlated with tumor formation latency.
- Rapidly tumorigenic cell lines exhibited undetectable p29 synthesis.
Conclusions:
- p29 synthesis is significantly reduced during fibroblast tumorigenic transformation.
- Decreased p29 levels are associated with advanced tumor progression.
- p29 may serve as a sensitive biomarker for fibroblast tumor progression.