Tumor suppressor p16INK4a determines sensitivity of human cells to transformation by cooperating cellular oncogenes
| Autor: | Janice Rowe, Darren Cuthbert-Heavens, Sarah Drayton, Gordon Peters, Rebecca Jones, Mike Fried, Radost Vatcheva, John Marshall |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Senescence
Telomerase Cancer Research Integrins Genes myc Locus (genetics) Biology medicine.disease_cause law.invention Mice Downregulation and upregulation law Tumor Suppressor Protein p14ARF medicine Cell Adhesion Animals Humans Telomerase reverse transcriptase Cyclin-Dependent Kinase Inhibitor p16 Cell Biology Neoplasms Experimental Fibroblasts Molecular biology DNA-Binding Proteins Cell Transformation Neoplastic Genes ras Oncology Karyotyping Cancer research Suppressor Ploidy Tumor Suppressor Protein p53 Carcinogenesis |
| Zdroj: | Cancer cell. 4(4) |
| ISSN: | 1535-6108 |
| Popis: | The Ink4a/Arf locus encodes two distinct proteins, both of which may contribute to senescence and tumor suppression. We find that human diploid fibroblasts (HDFs) that are specifically deficient for p16INK4a achieve anchorage independence when transduced with retroviruses encoding telomerase (hTERT) and either Ras or Myc. Significantly, Ras and Myc together enable the cells to form tumors in nude mice but at a frequency that suggests additional genetic changes. All five tumors analyzed expressed high levels of Ras and retained functional p53, although two showed downregulation of Arf. Cytogenetic analyses identified clonal chromosomal alterations that may have contributed to tumorigenesis, but the tumor cells were essentially diploid. |
| Databáze: | OpenAIRE |
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