Long-term cultured IL-2-dependent T cell lines demonstrate p16(INK4a) overexpression, normal pRb/p53, and upregulation of cyclins E or D2

Acquisition of an immortal phenotype by circumvention of the normal senesce nce program can be an important step in tumor development and progression. The regulation of life-span checkpoints is complex and abrogation of these processes can occur at different levels. To better understand these mechani sms in long-term cultured lymphocytes we have characterized two human long- term cultured IL-2-dependent T cell lines regarding telomere length, telome rase activity, and the expression of selected cell cycle regulators (pRb, p 53, cyclin E, cyclin D1, cyclin D2, cyclin D3, cdk4, p16(INK4a), p21(WAF1), p27(KIP1), c-myc, bcl-2, and NPAT). We compared these cell lines with a pr imary T lymphoblast population with a limited life span from the same donor . Both T cell lines with extraordinary growth capacity showed telomere leng th stabilization, high telomerase activity and demonstrated wild-type patte rn of pRb and p53 but strong p16(INK4a) protein expression. The growth inhi bitory activity of p16(INK4a) Seemed to be abrogated by enhanced expression of cyclin D2, cdk4, and c-myc in one T cell line and overexpression of cyc lin E in the second T cell line. (C) 2000 Elsevier Science Inc. All rights reserved.