Chromosomal instability and phenotypic plasticity during the squamous–spindle carcinoma transition: association of a specific T(14;15) with malignant progression View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2005-11

AUTHORS

Mar Pons, Juan C Cigudosa, Sandra Rodríguez-Perales, José L Bella, Cristina González, Carlos Gamallo, Miguel Quintanilla

ABSTRACT

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. More... »

PAGES

7608

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1208903

DOI

http://dx.doi.org/10.1038/sj.onc.1208903

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1023326739

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/16007119


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