title: FOXP3 over-expression inhibits melanoma tumorigenesis via effects on proliferation and apoptosis.
abstract: The Forkhead box P3 (FOXP3) transcription factor is the key driver of regulatory T cell (Treg cells) differentiation and immunosuppressive function. In addition, FOXP3 has been reported to be expressed in many tumors, including melanoma. However, its role in tumorigenesis is conflicting, with both tumor suppressive and tumor promoting functions described. The aim of the current study was to characterize the expression and function of FOXP3 in melanoma. FOXP3 expression was detected by immunohistochemistry (IHC) in 12% (18/146) of stage III and IV melanomas. However expression was confined to fewer than 1% of cells in these tumors. Stable over-expression of FOXP3 in the SK-MEL-28 melanoma cell line reduced cell proliferation and clonogenicity in vitro, and reduced xenograft growth in vivo. FOXP3 over-expression also increased pigmentation and the rate of apoptosis of SK-MEL-28 cells. Based on its infrequent expression in human melanoma, and its growth inhibitory and pro-apoptotic effect in over-expressing melanoma cells, we conclude that FOXP3 is not likely to be a key tumor suppressor or promoter in melanoma.
authors.affiliation: Ludwig Institute for Cancer Research Ltd. Melbourne-Austin Branch, Heidelberg, Victoria, Australia.
authors.forename: BeeShin
authors.initials: B
authors.lastname: Tan
authors.forename: Matthew
authors.initials: M
authors.lastname: Anaka
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Deb
authors.forename: Claudia
authors.initials: C
authors.lastname: Freyer
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ebert
authors.forename: Anderly C
authors.initials: AC
authors.lastname: Chueh
authors.forename: Sheren
authors.initials: S
authors.lastname: Al-Obaidi
authors.forename: Andreas
authors.initials: A
authors.lastname: Behren
authors.forename: Aparna
authors.initials: A
authors.lastname: Jayachandran
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.forename: John M
authors.initials: JM
authors.lastname: Mariadason
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D063646:Carcinogenesis; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D051858:Forkhead Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D014162:Transfection
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors