Drug-activated multiple pathways of defensin mRNA regulation in HL-60 cells are defined by reversed roles of participating protein kinases Journal Article
| Authors: | Herwig, S.; Su, Q.; Tempst, P. |
| Article Title: | Drug-activated multiple pathways of defensin mRNA regulation in HL-60 cells are defined by reversed roles of participating protein kinases |
| Abstract: | Defensin transcription in HL-60 promyelocytic leukemia cells is greatly enhanced during retinoic acid (RA)-induced differentiation. We have probed this regulatory pathway by selective modulation of various kinase activities. Induction was potentiated by elevated cAMP and attenuated by protein kinase C inhibition, entirely correlated to enhanced or blocked morphological differentiation, respectively. Yet, defensin mRNA was also induced in undifferentiated HL-60 cells, but not in others, by cAMP alone. By contrast, modulators that cooperated with RA had adverse effects on the normal capacity of dimethyl sulfoxide to upregulate these transcripts as well. Thus, defensin mRNA accumulation can be selectively uncoupled from maturation stage; and transcript levels may be regulated by multiple pathways, each independently acted upon by different chemical inducers. |
| Keywords: | human cell; antineoplastic agents; blood proteins; phenotype; enzyme inhibition; protein kinases; genetic transcription; cell differentiation; enzyme activity; protein tyrosine kinase; protein kinase inhibitors; leukemia, promyelocytic, acute; gene expression regulation, neoplastic; dimethyl sulfoxide; messenger rna; enzyme inhibitors; rna, messenger; promyelocytic leukemia; cyclic amp; protein kinase c; up-regulation; protein kinase; retinoic acid; granulocyte; cyclic amp dependent protein kinase; kinases; tretinoin; hl-60 cells; cell strain hl 60; defensin; defensins; humans; human; priority journal; article; granulocytic; blood bactericidal activity |
| Journal Title: | Leukemia Research |
| Volume: | 22 |
| Issue: | 10 |
| ISSN: | 0145-2126 |
| Publisher: | Elsevier Ltd |
| Date Published: | 1998-10-01 |
| Start Page: | 913 |
| End Page: | 925 |
| Language: | English |
| DOI: | 10.1016/s0145-2126(98)00086-1 |
| PUBMED: | 9766752 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 12 December 2016 -- Source: Scopus |
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