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.
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.
van der Stoep
Nienke
N
Division of Molecular Biology, Department of Immunohematology and Blood Transfusion, Building 1, E3-Q, Leiden University Medical Center, Albinusdreef 2, 2333 ZA Leiden, The Netherlands.
Quinten
Edwin
E
Alblas
Gabrielle
G
Plancke
Aurelie
A
van Eggermond
Marja C J A
MC
Holling
Tjadine M
TM
van den Elsen
Peter J
PJ
D000998:Antiviral Agents / Q000276:immunology / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D005802:Genes, MHC Class II / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D019169:Jurkat Cells; D008545:Melanoma / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020218:Response Elements / Q000276:immunology; D015534:Trans-Activators / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology
D000998:Antiviral Agents; C083728:MHC class II transactivator protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D007371:Interferon-gamma