Interferon-gamma upregulates MUC1 expression in haematopoietic and epithelial cancer cell lines, an effect associated with MUC1 mRNA induction.
Epithelial mucin-1 (MUC1) is an important target antigen that it is overexpressed in both epithelial and haematological cancers including multiple myeloma (MM) and some lymphomas and leukaemias. MUC1 has adhesive and immunosuppressive properties, which may promote cancer progression. These studies evaluated the effect of IFNs on MUC1 expression, since these agents are widely used in clinical cancer therapy. MUC1 and interferon (IFN) receptor expression were measured by radioligand binding. Changes in MUC1 mRNA levels in response to IFN-gamma were assessed by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). IFN-gamma was found to be a more potent inducer of MUC1 expression than IFN-alpha. 125I-IFN binding studies indicated that both IFN receptors were expressed in most of the cell lines. With IFN-gamma treatment, there was upregulation of MUC1 mRNA. IFN-gamma has a more consistent and more potent effect upon MUC1 induction than IFN-alpha. The ability to upregulate MUC1 across a broad range of cancer types by a clinically available cytokine, IFN-gamma, has important implications for enhancing immunotherapeutic approaches targeting MUC1.
Reddy
P K
PK
Center for Molecular Medicine and Immunology, 520 Belleville Avenue, Belleville, NJ 07109, USA.
Gold
D V
DV
Cardillo
T M
TM
Goldenberg
D M
DM
Li
H
H
Burton
J D
JD
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D002460:Cell Line; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D018396:Mucin-1 / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism*; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D017471:Receptors, Interferon / Q000378:metabolism; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D018396:Mucin-1; D012333:RNA, Messenger; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D007371:Interferon-gamma