Restoring the apoptosis suppression response to IL-5 confers on erythroleukemic cells a phenotype of IL-5-dependent growth.
We have established a human IL-5 (hIL-5) dependent cell line, JYTF-1, derived from TF-1 parental human erythroleukemic cells by long-term cultivation in the presence of hIL-5. The ED50 values of hIL-5 for both TF-1 and JYTF-1 cell lines remained similar. However, when cells were grown in an optimal concentration of IL-5, some TF-1 cells but not JYTF-1 cells died via apoptosis. Although the rates of DNA synthesis were similar for TF-1 and JYTF-1 cells grown in IL-5, [3-H]thymidine releasing of pulse-labeled DNA analysis indicated that the viable TF-1 cells in IL-5 were more apoptosis-prone than were JYTF-1 cells. Therefore, in the JYTF-1 variant, the ability to suppress apoptosis has apparently been restored. The following findings suggest that overexpression of the hIL-5 receptor alpha-chain may be responsible for restoring the apoptosis suppression ability of IL-5: 1) the growth of JYTF-1 cells remained cytokine-dependent; 2) the proliferation of JYTF-1 cells in IL-5 was not mediated by autocrine secretion; 3) JYTF-1 and TF-1 cells responded similarly to other cytokines such as human erythropoietin; 4) Northern blot analysis revealed that JYTF-1 cells expressed approximately eightfold more IL-5 receptor alpha-chain mRNA than did TF-1. To our knowledge, JYTF-1 represents the first example in which coupling of mitogenesis stimulation and apoptosis suppression from otherwise uncoupled parental cells confers a phenotype of IL-5-dependent growth.
Yen
J J
JJ
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
Hsieh
Y C
YC
Yen
C L
CL
Chang
C C
CC
Lin
S
S
Yang-Yen
H F
HF
D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000096:biosynthesis; D015870:Gene Expression; D006801:Humans; D015848:Interleukin-5 / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008969:Molecular Sequence Data; D010641:Phenotype; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics; D053649:Receptors, Interleukin-5; D013936:Thymidine / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism / Q000473:pathology
D017931:DNA Primers; D004273:DNA, Neoplasm; D015848:Interleukin-5; D016187:Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5; D013936:Thymidine