Over expression of insulin-like growth factor receptor type-I in T-cell lines infected with human T-lymphotropic virus types-I and -II.
To determine if aberrant expression of tyrosine kinase growth factor receptors may be related to the cell transformation capabilities of human T-lymphotropic viruses (HTLVs), we examined the expression of the epidermal growth factor receptor (EGF-R), insulin receptor (INS-R), and insulin-like growth factor receptor type-I (IGFR-I) in cell lines infected with HTLV type I (MT-2, HuT-102) and HTLV type II (Mo-T). Levels of mRNA transcripts for IGFR-I were significantly higher in both MT-2, HuT-102 (HTLV-I) and Mo-T (HTLV-II) cell lines than in uninfected cell lines (HuT-78, Jurkat); no detectable levels of EGF-R or INS-R mRNA transcript were observed in HTLV-infected or uninfected cell lines. Southern blot analysis demonstrated that no amplification or rearrangement of the IGFR-I gene occurred in either the MT-2 or Mo-T cell line. Flow cytometry analysis demonstrated that while IGFR-I protein was constitutively expressed on the cell surface in both MT-2 and Mo-T cell lines, neither EGF-R nor INS-R proteins could be detected. Ligand binding studies with MT-2 and Mo-T cell lines demonstrating binding of 125I insulin-like growth factor type-1 (IGF-I) in a dose-dependent manner and this response could be inhibited by increasing concentrations of cold IGF-I. These data demonstrate that deregulated expression of functional IGFR-I, the regular component of the growth control machinery of normal cells, may contribute to cellular proliferation and eventual transformation in HTLV-I- and HTLV-II-infected cell lines.
Lal
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Retrovirus Diseases Branch, Centers for Disease Control, Atlanta, GA 30333.
Rudolph
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DL
Folks
T M
TM
Hooper
W C
WC
D002472:Cell Transformation, Viral; D066246:ErbB Receptors / Q000032:analysis; D015491:HTLV-II Infections / Q000378:metabolism; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D015367:Human T-lymphotropic virus 2 / Q000502:physiology*; D006801:Humans; D007943:Leukemia, Hairy Cell / Q000378:metabolism; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D011972:Receptor, Insulin / Q000032:analysis; D013601:T-Lymphocytes / Q000737:chemistry* / Q000382:microbiology*; D014407:Tumor Cells, Cultured
D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin