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Interleukin-2 expression in human carcinoma cell lines and its role in cell cycle progression.
- Source :
-
Oncogene [Oncogene] 2000 Jan 27; Vol. 19 (4), pp. 514-25. - Publication Year :
- 2000
-
Abstract
- Human carcinomas were shown to express mRNA and protein for IL-2R alpha, beta and gamma chains. Recently, human carcinomas were also shown to constitutively express protein and mRNA for IL-2 in vivo and in vitro. Here we report that the expression levels of cytoplasmic IL-2 as well as IL-2Rbeta- and gamma-chain in human carcinoma cells change during the cell cycle progression. Carcinoma cells synchronized in the G2/M phase of the cell cycle expressed significantly more intracytoplasmic IL-2 as well as IL-2Rbeta and gamma 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 p27kip1 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 the 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 in tumor cells, we observed increased levels of p27 as well as p21. The antisense 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.
- Subjects :
- Blotting, Western
Carcinoma genetics
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21
Cyclin-Dependent Kinase Inhibitor p27
Cyclins biosynthesis
Cyclins genetics
Humans
Immunoenzyme Techniques
Interleukin-2 genetics
Interleukin-2 physiology
Jurkat Cells metabolism
Jurkat Cells pathology
Keratinocytes cytology
Keratinocytes metabolism
Microtubule-Associated Proteins biosynthesis
Microtubule-Associated Proteins genetics
Neoplasm Proteins genetics
Neoplasm Proteins physiology
Oligonucleotides, Antisense pharmacology
RNA, Messenger biosynthesis
RNA, Neoplasm biosynthesis
Receptors, Interleukin-2 genetics
Receptors, Interleukin-2 physiology
Reverse Transcriptase Polymerase Chain Reaction
T-Lymphocytes cytology
T-Lymphocytes metabolism
Tumor Cells, Cultured
Carcinoma pathology
Cell Cycle genetics
Cell Cycle Proteins
Gene Expression Regulation, Neoplastic drug effects
Interleukin-2 biosynthesis
Neoplasm Proteins biosynthesis
Receptors, Interleukin-2 biosynthesis
Tumor Suppressor Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0950-9232
- Volume :
- 19
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 10698521
- Full Text :
- https://doi.org/10.1038/sj.onc.1203391