Abstract / Description of output
Ras proteins transduce signals from membrane-bound receptors via multiple downstream effector pathways and thereby affect fundamental cellular processes, including proliferation, apoptosis, and differentiation. K-ras activating mutations play a key role in neoplastic progression and are particularly prevalent in colorectal, pancreatic, and lung cancers. The present study addressed whether the K-ras proto-oncogene displays a tumor suppressor function by comparative analysis of mouse teratomas derived from wild-type embryonic stem (ES) cells, K-ras null (K-ras(-/-)) ES cells, and K-ras(-/-) ES cells that stably reexpress either wild-type K-ras(gly12) or oncogenic K-ras(val12). K-ras(-/-) and K-ras(val12) teratomas were significantly larger than teratomas that expressed wild-type K-ras, contained significantly higher proportions of undifferentiated embryonal carcinoma-like cells, and showed significantly increased mitotic activity. However, K-ras(val12) but not K-ras(-/-) teratomas exhibited significantly higher levels of apoptosis than wild-type teratomas. K-ras(-/-) and K-ras(val12) ES cells showed a higher capacity for stem cell self-renewal in vitro compared with wild-type ES cells, and reexpression of K-ras(gly12) in K-ras(-/-) ES cells restored the K-ras(-/-) phenotype to wild-type values. Thus, in view of evidence that tumors can derive from tissue stem cells and that tumors harbor "cancer stem cells," aberrant K-ras expression could promote neoplastic progression by increasing their capacity for self-renewal.
Original language | English |
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Pages (from-to) | 820-5 |
Number of pages | 6 |
Journal | Molecular Cancer Research |
Volume | 1 |
Issue number | 11 |
Publication status | Published - Sept 2003 |
Keywords / Materials (for Non-textual outputs)
- Animals
- Cell Differentiation
- Female
- Gene Deletion
- Genes, Tumor Suppressor
- Genes, ras
- Genotype
- Mice
- Mitosis
- Stem Cells
- Teratoma