Cell cycle-dependent expression of TAP1, TAP2, and HLA-B27 messenger RNAs in a human breast cancer cell line.
Tumor cells are generally poorly responsive to immunotherapy. The results presented here suggest that antigen presentation of somatic tumor cells may be diminished greatly in quiescence and may be determined in part by growth regulation. Peptides produced by proteasomes are transported into the endoplasmic reticulum by transporter proteins TAP-1 and TAP-2, where they bind and stabilize MHC class I molecules required for antigenic presentation on the cell surface. TAP-1 and TAP-2 mRNAs were undetectable in quiescent, serum-deprived human breast cancer cells (21PT). They appeared 10 h after serum induction, near the G(1)-S boundary. In contrast, HLA-B27 mRNA was biphasically up-regulated. These mRNAs were significantly down-regulated in most tissues that contain mainly terminally differentiated, nonproliferating cells. All of the investigated breast cancer cell lines showed lower expression levels of these mRNAs than did the corresponding normal cells.
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Division of Cell Growth and Regulation, Dana-Farber Cancer Institute, Department of Biological Chemistry, Harvard Medical School, Boston, Massachusetts 02115, USA.
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Pardee
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D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis / Q000235:genetics*; D017951:Antigen Presentation; D000951:Antigens, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D001940:Breast / Q000166:cytology / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle / Q000235:genetics*; D002455:Cell Division; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015796:HLA-B27 Antigen / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
D000071181:ATP Binding Cassette Transporter, Subfamily B, Member 2; D000071450:ATP Binding Cassette Transporter, Subfamily B, Member 3; D018528:ATP-Binding Cassette Transporters; D000951:Antigens, Neoplasm; D016895:Culture Media, Serum-Free; D015796:HLA-B27 Antigen; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C073119:TAP1 protein, human; C071692:TAP2 protein, human