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 senescence 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 mechanisms in long-term cultured lymphocytes we have characterized two human long-term cultured IL-2-dependent T cell lines regarding telomere length, telomerase activity, and the expression of selected cell cycle regulators (pRb, p53, 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 primary T lymphoblast population with a limited life span from the same donor. Both T cell lines with extraordinary growth capacity showed telomere length stabilization, high telomerase activity and demonstrated wild-type pattern of pRb and p53 but strong p16(INK4a) protein expression. The growth inhibitory 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 cyclin E in the second T cell line.
Siwicki
J K
JK
Department of Immunology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
Hedberg
Y
Y
Nowak
R
R
Lodén
M
M
Zhao
J
J
Landberg
G
G
Roos
G
G
D018929:Cell Culture Techniques / Q000379:methods; D002453:Cell Cycle; D002460:Cell Line; D056742:Cyclin D2; D019927:Cyclin E / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism*; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000378:metabolism*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C080336:CCND2 protein, human; D056742:Cyclin D2; D019927:Cyclin E; D019941:Cyclin-Dependent Kinase Inhibitor p16; D016213:Cyclins; D007376:Interleukin-2; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; D019098:Telomerase