Constitutive and IFNgamma-induced activation of MHC2TA promoter type III in human melanoma cell lines is governed by separate regulatory elements within the PIII upstream regulatory region.
ABSTRACT Cell lines established from tumor tissue of cutaneous melanoma biopsies often display constitutive and IFNgamma-inducible expression of MHC class II molecules. The expression of MHC class II molecules in melanoma is associated with an overall poor prognosis and unfavorable clinical outcome. We have analyzed the DNA elements and interacting transcription factors that control the constitutive and IFNgamma-inducible expression of the class II transactivator (CIITA), a co-activator essential for transcription of all MHC class II genes. Our studies reveal the activation of multiple CIITA promoter regions (CIITA-PII, -PIII and -PIV) in melanoma cell lines for both the constitutive and IFNgamma-inducible expression of MHC class II molecules. Furthermore, we show that constitutive and IFNgamma-inducible expression of the CIITA-PIII isoform is governed by separate regulatory elements within the PIII upstream regulatory region (PURR). Similarly constitutive activation in melanoma of CIITA-PII, CIITA-PIII, and CIITA-PIV does not require components of the IFNgamma signaling pathway. However, these components are readily recruited to the PURR and CIITA-PIV after exposure of cells to IFNgamma and account for the IFNgamma-induced expression of CIITA. Together, our data reveal the contribution of distinct elements and factors in the constitutive and IFNgamma-inducible expression of CIITA in melanoma cell lines of the skin.
- SourceAvailable from: Edgar Wingender[show abstract] [hide abstract]
ABSTRACT: TRANSFAC, TRRD (Transcription Regulatory Region Database) and COMPEL are databases which store information about transcriptional regulation in eukaryotic cells. The three databases provide distinct views on the components involved in transcription: transcription factors and their binding sites and binding profiles (TRANSFAC), the regulatory hierarchy of whole genes (TRRD), and the structural and functional properties of composite elements (COMPEL). The quantitative and qualitative changes of all three databases and connected programs are described. The databases are accessible via WWW:http://transfac.gbf.de/TRANSFAC orhttp://www.bionet.nsc.ru/TRRDNucleic Acids Research 02/1998; 26(1):362-7. · 8.28 Impact Factor
Article: Pathology and prognostic factors.[show abstract] [hide abstract]
ABSTRACT: Cutaneous malignant melanoma and its precursors were the general subjects of the National Institutes of Health Consensus Conference held in January 1992. Particular emphasis was placed on the diagnosis of early melanoma, especially melanoma in situ, and the controversies surrounding dysplastic nevi. Recent studies of unusual nevi often confused with melanoma, eg, deep-penetrating (plexiform) nevus, combined nevus, desmoplastic melanocytic nevus, and Spitz nevus in childhood, provided detailed histologic criteria for their discrimination from melanoma. Rare or unusual forms of melanoma, including desmoplastic melanoma, neurotropic melanoma, a newly described variant angiotrophic melanoma, subungual melanoma, and balloon cell melanoma have been the subject of comprehensive histologic studies. Other histopathologic investigations have described the prevalence of histologic regression and intraepidermal pagetoid spread in melanomas and the histologic features of reexcision specimens of melanoma. New evidence suggests that the predominant cell type infiltrating melanoma is the monocyte-macrophage, and the expression of monocyte chemotactic protein-1 by melanoma may explain the recruitment of this cell type. Immunopathologic studies of melanocytic lesions were performed with various melanocyte-associated antigens (eg, HMB-45), proliferation antigens (eg, Ki-67), and progression markers (eg, epidermal growth factor receptor and HLA-DR). HMB-45 binding has been localized ultrastructurally to early melanosome formation. Various prognostic factors, including gender, high-risk anatomic sites (particularly the scalp), race (black vs white patients), microscopic satellites, tumor volume, indices of proliferation and tumor cell motility, volume-weighted mean nuclear volume, DNA ploidy, and nucleolar organizer regions have been the subject of recent investigations. Analysis of many patients with long-term follow-up has facilitated better prognostic modeling of melanoma.Current Opinion in Oncology 04/1993; 5(2):364-76. · 4.03 Impact Factor
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ABSTRACT: MHC class I and class II molecules play essential roles in the adaptive immune response by virtue of their ability to present peptides to T lymphocytes. Given their central role in adaptive immunity, the genes encoding these peptide-presenting molecules are regulated in a tight fashion to meet with local requirements for an adequate immune response. In contrast to MHC class I gene products, which are expressed on almost all nucleated cells, constitutive expression of MHC class II molecules is found only in specialized antigen-presenting cells of the immune system. Expression of both classes of MHC molecules can be induced by immune regulators and upon cell activation. A set of conserved cis-acting regulatory promoter elements mediate the transcription of MHC class I and beta2-microglobulin genes. Of these regulatory elements, the promoters of MHC class II and accessory genes also have the SXY module. The MHC class II transactivator (CIITA) is essential for the activation of MHC class II promoters, and it functions through protein-protein interactions with regulatory factors bound to the SXY module. Given the central role of CIITA in these regulatory processes, it is of interest to identify the DNA-binding factors and co-activators that assemble on CIITA promoters in a cell-type-specific fashion. Accordingly, recent studies include investigations into chromatin remodeling and epigenetic control mechanisms that modulate cell-type-specific transcriptional regulation of genes involved in antigen presentation.Current Opinion in Immunology 03/2004; 16(1):67-75. · 8.77 Impact Factor