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Expression of tie receptor tyrosine kinase in leukemia cell lines
E Armstrong1, J Korhonen, O Silvennoinen
1Department of Pathology, University of Helsinki, Finland.
Abstract:
The tie receptor tyrosine kinase mRNA was originally identified as an amplified product in reverse transcription-polymerase chain reaction analysis of human K562 leukemia cell RNA. In situ hybridization analysis revealed that the corresponding mouse gene is expressed predominantly in endothelial cells. We have explored tie mRNA and protein expression in tumor cell lines. The 4.4 kb tie mRNA was expressed at high levels in five of five human megakaryoblastic leukemia cell lines studied and in two IL-3-dependent mouse myeloid leukemia cell lines, but not in 42 other leukemia cell lines representing various hematopoietic lineages. Increased expression of tie mRNA and protein was observed upon treatment of the megakaryoblastic leukemia cells with the tumor promoter 12-0-tetradecanoyl-phorbol-13-acetate (TPA), known to enhance megakaryoblastic markers. Among several cell lines from solid tumors, two fibrosarcomas, one rhabdomyosarcoma and one melanoma cell line were positive for tie mRNA. These results suggest that among hematopoietic lineages tie is predominantly expressed in cells with megakaryoblastic properties and that the tie tyrosine kinase is a receptor for a regulatory factor specific for megakaryoblasts, endothelial cells, and occasional tumor cell lines derived from mesenchymal tissues.
Insights
The tie tyrosine kinase receptor is primarily found in megakaryoblastic leukemia cells and endothelial cells. Its expression increases with TPA treatment, suggesting a role in megakaryoblast development and certain tumors.
Area of Science:
- Molecular Biology
- Oncology
- Cell Biology
Background:
- The tie receptor tyrosine kinase (RTK) was initially identified in human K562 leukemia cells.
- In situ hybridization showed predominant mouse tie gene expression in endothelial cells.
Purpose of the Study:
- To investigate tie mRNA and protein expression in various tumor cell lines.
- To determine the specificity of tie expression within hematopoietic lineages and solid tumors.
Main Methods:
- Reverse transcription-polymerase chain reaction (RT-PCR) for mRNA detection.
- In situ hybridization for gene expression localization.
- Analysis of tie expression in human and mouse leukemia cell lines and solid tumor cell lines.
- Assessment of tie expression following treatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA).
Main Results:
- High levels of 4.4 kb tie mRNA were found in all five human megakaryoblastic leukemia cell lines and two IL-3-dependent mouse myeloid leukemia cell lines.
- Tie mRNA and protein expression increased in megakaryoblastic cells upon TPA treatment.
- Tie mRNA was detected in two fibrosarcomas, one rhabdomyosarcoma, and one melanoma cell line.
- Tie was not expressed in 42 other leukemia cell lines from various hematopoietic lineages.
Conclusions:
- Tie is predominantly expressed in hematopoietic cells with megakaryoblastic properties.
- The tie tyrosine kinase may act as a receptor for a regulatory factor specific to megakaryoblasts and endothelial cells.
- Tie expression is also observed in some tumor cell lines derived from mesenchymal tissues.