Abstract
Acquisition of the immortal phenotype by tumor cells represents an essential and potentially rate-limiting step in tumorigenesis. To identify changes in gene expression that are associated with the early stages of cell immortalization, we compared genetically matched pairs of pre-immortal and immortal human cell clones by mRNA differential display. Two transcripts, denoted CIR1 and CIR2, were identified which were up-regulated in immortal cells. Sequence analysis revealed CIR1 to be identical to the recently cloned CROC1/UEV-1 gene, whereas CIR2 corresponds to an as yet uncharacterized 1.2âkb mRNA. A 5â6-fold elevation in CIR1/CROC1 expression and a 2â3-fold elevation in CIR2 expression were observed in SV40-transformed human enbryonic kidney cells immediately following proliferative crisis, suggesting a potential role for these genes in immortalization. Expression of CIR1/CROC1 was found to be elevated also in a variety of immortal human tumor-derived cell lines, as compared to their normal tissue counterparts. These results are compatible with induction of CIR1/CROC1 being an early event in the acquisition of immortality and with a role for this gene in the immortal phenotype of tumor cells.
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Ma, L., Broomfield, S., Lavery, C. et al. Up-regulation of CIR1/CROC1 expression upon cell immortalization and in tumor-derived human cell lines. Oncogene 17, 1321â1326 (1998). https://doi.org/10.1038/sj.onc.1202058
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DOI: https://doi.org/10.1038/sj.onc.1202058
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