title: The human TCF-1 gene encodes a nuclear DNA-binding protein uniquely expressed in normal and neoplastic T-lineage lymphocytes.
abstract: The TCF-1 gene encodes a putative transcription factor with affinity for a sequence motif occurring in a number of T-cell enhancers. TCF-1 mRNA was originally found to be expressed in a T cell-specific fashion within a set of human and mouse cell lines. In contrast, expression reportedly occurs in multiple nonlymphoid tissues during murine embryogenesis. We have now raised a monoclonal antibody to document expression and biochemistry of the human TCF-1 protein. As expected, the TCF-1 protein was detectable only in cell lines of T lineage. Its expression was always restricted to the nucleus. Immunohistochemistry on a panel of human tissues revealed that the TCF-1 protein was found exclusively in thymocytes and in CD3+ T cells in peripheral lymphoid tissues. Western blotting yielded a set of bands ranging from 25 kD to 55 kD, resulting from extensive alternative splicing. The TCF-1 protein was detectable in all samples of a set of 22 T-cell malignancies of various stages of maturation, but was absent from a large number of other hematologic neoplasms. These observations imply a T cell-specific function for TCF-1, a notion corroborated by recent observations on Tcf-1 knock-out mice. In addition, these results indicate that nuclear TCF-1 expression can serve as a pan-T-lineage marker in the diagnosis of lymphoid malignancies.
authors.affiliation: Department of Immunology, University Hospital Utrecht, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Castrop
authors.forename: D
authors.initials: D
authors.lastname: van Wichen
authors.forename: M
authors.initials: M
authors.lastname: Koomans-Bitter
authors.forename: M
authors.initials: M
authors.lastname: van de Wetering
authors.forename: R
authors.initials: R
authors.lastname: de Weger
authors.forename: J
authors.initials: J
authors.lastname: van Dongen
authors.forename: H
authors.initials: H
authors.lastname: Clevers
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015415:Biomarkers; D014408:Biomarkers, Tumor / Q000032:analysis*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D005796:Genes; D051538:Hepatocyte Nuclear Factor 1-alpha; D006801:Humans; D007279:Injections, Subcutaneous; D015458:Leukemia, T-Cell / Q000378:metabolism*; D051821:Lymphoid Enhancer-Binding Factor 1; D016399:Lymphoma, T-Cell / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*; D012326:RNA Splicing; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D051822:T Cell Transcription Factor 1; D013601:T-Lymphocytes / Q000378:metabolism*; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D015415:Biomarkers; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D051538:Hepatocyte Nuclear Factor 1-alpha; C496488:Hnf1a protein, mouse; D051821:Lymphoid Enhancer-Binding Factor 1; D009363:Neoplasm Proteins; D011993:Recombinant Fusion Proteins; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; D014157:Transcription Factors