UP-REGULATION OF CIR1 CROC1 EXPRESSION UPON CELL IMMORTALIZATION AND IN TUMOR-DERIVED HUMAN CELL-LINES/

Acquisition of the immortal phenotype by tumor cells represents an ess ential and potentially rate-limiting step in tumorigenesis, To identif y 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 id entical to the recently cloned CROC1/UEV-1 gene, whereas CIR2 correspo nds to an as yet uncharacterized 1.2 kb mRNA, A 5-6-fold elevation in CIR1/CROC1 expression and a 2-3-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 el evated also in a variety of immortal human tumor-derived cell lines, a s compared to their normal tissue counterparts. These results are comp atible with induction of CIR1/CROC1 being an early event in the acquis ition of immortality and with a role for this gene in the immortal phe notype of tumor cells.