title: Select cancer testes antigens of the MAGE-A, -B, and -C families are expressed in mast cell lines and promote cell viability in vitro and in vivo.
abstract: MAGE antigens are proteins that are normally expressed only in gametes but are often aberrantly expressed in melanomas, hematopoietic malignancies, and other "cancers". The functions of most MAGE proteins are unknown. Data have accumulated suggesting expression of MAGE proteins by malignant cells may contribute to advanced disease or resistance to chemotherapy, but direct evidence supporting this hypothesis is lacking. We show here that small interfering RNA (siRNA) suppression of MAGE-A, -B, and -C gene expression slows proliferation and induces caspase independent apoptosis in human and murine mast cell lines. Furthermore, treatment with MAGE specific siRNA suppresses growth of malignant cells in an in vivo murine model of mastocytosis. These observations demonstrate that MAGE protein expression can contribute to the development of tumors by permitting proliferation and prolonging the survival of malignant cells. We suggest a shift of the current clinical paradigm from one that envisions MAGE proteins solely as targets for immunologic attack to one in which MAGE genes and proteins are also targets for functional manipulation.
authors.affiliation: Department of Dermatology, University of Wisconsin Medical School, Madison, Wisconsin 53706, USA. byang@dermatology.wisc.edu
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.forename: Sean
authors.initials: S
authors.lastname: O'Herrin
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Wu
authors.forename: Shannon
authors.initials: S
authors.lastname: Reagan-Shaw
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Ma
authors.forename: Minakshi
authors.initials: M
authors.lastname: Nihal
authors.forename: B Jack
authors.initials: BJ
authors.lastname: Longley
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D008415:Mastocytosis / Q000473:pathology; D051379:Mice; D008811:Mice, Inbred DBA; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D034741:RNA, Small Interfering / Q000494:pharmacology; D013737:Testis / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D020169:Caspases