Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression

Human carcinomas were shown to express mRNA and protein for IL-2R alpha, be ta and gamma chains. Recently, human carcinomas were also shown to constitu tively express protein and mRNA for IL-2 in vivo and in vitro. Here ape rep ort that the expression levels of cytoplasmic IL-2 as well as IL-2R beta- a nd gamma-chain in human carcinoma cells change during the cell cycle progre ssion, Carcinoma cells synchronized in the G2/M phase of the cell cycle exp ressed significantly more intracytoplasmic IL-2 as web as IL-2R beta and ga mma proteins than tumor cells in the G0/G1 phase, The level of mRNA for IL- 2 was 5-10-fold higher in the M phase than in the G0/G1-phase, as shown by quantitative competitive RT-PCR, Expression of the cyclin-dependent kinase (CDK) inhibitor p27(kip1) in these carcinoma cells was found to be high in the G0/G1 phase, nearly absent in the S phase, and it increased again in th e G2/M phase of the cell cycle, In synchronized cells, the decrease in p27 expression coincided with high levels of expression of IL-2. Using the IL-2 specific antisense oligonucleotide to block synthesis of endogenous IL-2 i n tumor cells, we observed increased levels of p27 as well as p21. The anti sense oligonucleotides specific for p27 or p21 blocked expression of these proteins but not of IL-2. Thus, endogenous IL-2 is important in regulating expression of p27 as well as p21 and, therefore, in controlling cell cycle progression of tumor cells, while its own expression remains independent of the CDK inhibitors.