Quantitative analysis of CD5 antigen modulation by 12-O-tetradecanoylphorbol-13-acetate in T-lymphoblastic leukemia cells: individual response patterns and their relationships with both maturation and protein kinase C content.
Modulation of CD5 expression by TPA was investigated on T-leukemic cell lines corresponding to different stages of ontogeny. These CD5 changes have been analyzed simultaneously with modifications of cell growth, cell cycle, cell surface phenotype, and PKC content. CD5 expression was found 6- to 17-fold increased by TPA in a dose-dependent manner on phenotypically mature T-cells (Jurkat, JM, and T-CLL) while T-cells from earlier stages of differentiation (CEM III, CEM 95, and CEM 44) were found unresponsive. CD5 upregulation on TPA-sensitive JM cells appears correlated with inhibition of cell growth, blockage in G1 phase, and phenotypic maturation (downregulation of CD7 and CD1 antigens) and seemed to be related to PKC activation since DiC8 (a PKC activator) mimicked this TPA effect and H7 (a PKC inhibitor) partially reduced it. On the other hand, on CEM III cells TPA induced no modulation of CD5 antigen, a less dramatic effect on cell growth and cell cycle, but a CD7 downregulation. TPA appeared fully effective in binding and translocating PKC in both CEM III and JM cells, although the PKC activity level was three times higher in the latter. Finally, our study suggests that CD5 expression is at least partially under control of PKC in phenotypically mature neoplastic T-cells while PKC could not be directly involved in the regulation of CD5 antigen in leukemic cells arrested at earlier stages of differentiation.
Laboratoire de Pharmacologie et de Toxicologie Fondamentales CNRS 0029 Toulouse, France.
M
M
Chiron
J M
JM
Darbon
F
F
Roubinet
G
G
Cassar
J P
JP
Jaffrezou
C
C
Bordier
G
G
Laurent
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000943:Antigens, Differentiation / Q000378:metabolism*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D018956:CD5 Antigens; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D004075:Diglycerides / Q000494:pharmacology; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007546:Isoquinolines; D015458:Leukemia, T-Cell / Q000378:metabolism*; D010641:Phenotype; D010879:Piperazines; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018956:CD5 Antigens; D004075:Diglycerides; D007546:Isoquinolines; D010879:Piperazines; C044295:1,2-dioctanoylglycerol; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate