title: Tumor necrosis factor receptor superfamily member TROY is a novel melanoma biomarker and potential therapeutic target.
abstract: Incidence of melanoma continues to rise, and a better understanding of its genetics will be critical to improve diagnosis and develop new treatments. Here, we search for novel melanoma-specific genes that may serve as biomarkers and therapeutic targets by using an in vitro genetic screen. One identified cDNA encoded TROY, a member of the tumor necrosis factor receptor superfamily (TNFRSF). TROY is widely expressed during embryogenesis, but in adults expression is restricted to hair follicles and brain. However, TROY had never been associated with melanoma, and it was selected for further study. First we show that expression in melanoma is specific by semiquantitative RT-PCR analysis of a large panel of established tumor cell lines. Next, specificity of expression was evaluated by immunohistochemistry analysis of primary cell cultures and patient tissues. TROY is expressed in 2/2 primary melanoma cells and 45/45 melanoma tissue samples (p < 0.0001). With the exception of sebaceous glands, TROY is not expressed in normal skin biopsies (p < 0.0001) or primary skin cell cultures that contain keratinocytes and epidermal melanocytes, nor is it expressed in other skin tumor cells (p < 0.0001). Finally, we show that TROY regulates melanoma growth, because replication of melanoma cells with reduced TROY levels through treatment with short-interfering RNA was significantly decreased relative to control cells (p < 0.004). In summary, TROY is the first TNFRSF member that is a biomarker for melanoma. TROY also presents a potentially novel cell surface signaling target for inhibitors, cell and/or antibody-based immunotherapies.
authors.affiliation: Department of Otolaryngology, Cancer Research Center, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA. rspan@bu.edu
authors.forename: Remco A
authors.initials: RA
authors.lastname: Spanjaard
authors.forename: Kara M
authors.initials: KM
authors.lastname: Whren
authors.forename: Carole
authors.initials: C
authors.lastname: Graves
authors.forename: Jag
authors.initials: J
authors.lastname: Bhawan
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008544:Melanocytes / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D008545:Melanoma / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D012878:Skin Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D048029:TNF Receptor-Associated Factor 6 / Q000032:analysis / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D048029:TNF Receptor-Associated Factor 6; C411850:TNFRSF19 protein, human; D014212:Tretinoin