Reversion of UVC-induced tumorigenic human hybrid cells to the non-tumorigenic phenotype

Autor: C. Sun, J.L. Redpath, R.J. Antonionio
Rok vydání: 1996
Předmět:
Zdroj: European journal of cancer (Oxford, England : 1990). (2)
ISSN: 0959-8049
Popis: Non-tumorigenic HeLa x skin fibroblast human hybrid cells were UVC-irradiated (10 J/m2) and induced to neoplastic transformation with accompanying morphological change and expression of the HeLa tumour-associated antigen, intestinal alkaline phosphatase (IAP). A single-cell-derived cell line was cloned out of a neoplastically transformed focus and designated as UV-12. In low density culture, this cell line demonstrated the ability to undergo reversion to a morphology similar to that of the nontumorigenic parent with accompanying, much reduced levels of LAP expression. The frequency of this reversion to low LAP expression increased with passage of low density cultures reaching 10−2 at 26 passages. A revertant colony was selected and expanded into a cell line which was designated UV-12-RM-1. This cell line had a 67-fold reduction in LAP expression compared to UV-12 and demonstrated a much reduced tumorigenic phenotype. A cell line reconstituted from a tumour derived from this cell line demonstrated a high LAP expression level (3-fold less than UV-12) and was highly tumorigenic. Six single-cell-derived lines were cloned from UV-12-RM-1 and all had low LAP expression. Of these, one demonstrated an aggressive tumorigenicity, four showed the reduced tumorigenic phenotype characteristic of UV-12-RM-1, and one (UV-12-RM-105) was non-tumorigenic. However, with passage in culture, this latter cell line reverted to a weakly tumorigenic phenotype and a much elevated IAP level. It is hypothesised that the phenotypic shifts demonstrated by these UV-induced tumorigenic cells are under epigenetic control, and that they are most likely a consequence of an underlying genetic instability in the survivors of UVC-irradiation.
Databáze: OpenAIRE
Externí odkaz: