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Título: | Chromosomal instability and phenotypic plasticity during the squamous-spindle carcinoma transition: Association of a specific T(14;15) with malignant progression |
Autor: | Pons, Mar CSIC; Cigudosa, Juan C.; Gónzalez, Cristina; Gamallo, Carlos; Quintanilla, Miguel CSIC ORCID | Fecha de publicación: | 2005 | Editor: | Nature Publishing Group | Citación: | Oncogene 24(51): 7608-7618 (2005) | Resumen: | In mouse epidermal carcinogenesis, the latest stage of malignant progression involves the transition from squamous cell carcinoma to a highly aggressive type of tumor with spindle morphology. In this work, we have isolated a minor epithelial cell subpopulation (CarC-R) contained in the highly malignant spindle carcinoma cell line CarC. CarC-R exhibited a drastic reduction in tumorigenicity when compared with CarC, but CarC-R-induced tumors were mainly sarcomatoid, although they subsequently reverted to the epithelial phenotype when tumor explants were recultured in vitro. Several single-cell clones with either stable epithelial or fibroblastic phenotypes were isolated from an explanted CarC-R tumor (CarC-RT). All these cell lines contained the same specific point mutation in H-Ras codon 61, but while CarC spindle cells had lost the normal H-Ras allele, it was retained in CarC-R- and CarC-RT-derived cell lines. Furthermore, CarC cells have inactivated p16INK4a and p19INK4a/ARF transcription, while CarC-R and CarC-RT clones expressed p19 mRNA and protein but not p16. Altogether, these results suggest that CarC-R represents a precursor stage to CarC in malignant progression. Spectral karyotyping analysis revealed that CarC-R was highly aneuploid and contained many chromosomal abnormalities. In contrast, CarC had a diploid or tetraploid modal chromosome number and contained a specific T(14;15) translocation in all of the analysed metaphases. The T(14;15) translocation was present in only a minority (1.9%) of CarC-R cells, but it was widely spread in CarC-RT and its derived cell clones, regardless of their epithelial or fibroblastic phenotype, indicating that T(14;15) segregates with malignancy. © 2005 Nature Publishing Group All rights reserved. | Descripción: | El pdf del artículo es la versión post-print.-- et al. | Versión del editor: | http://dx.doi.org/10.1038/sj.onc.1208903 | URI: | http://hdl.handle.net/10261/81249 | DOI: | 10.1038/sj.onc.1208903 | Identificadores: | doi: 10.1038/sj.onc.1208903 issn: 0950-9232 e-issn: 1476-5594 |
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