title: The regulatory T cell-associated transcription factor FoxP3 is expressed by tumor cells.
abstract: FoxP3 is a member of the forkhead family of transcription factors critically involved in the development and function of CD25(+) regulatory T cells (Treg). Until recently, FoxP3 expression was thought to be restricted to the T-cell lineage. However, using immunohistochemistry and flow cytometric analysis of human melanoma tissue, we detected FoxP3 expression not only in the tumor infiltrating Treg but also in the melanoma cells themselves. FoxP3 is also widely expressed by established human melanoma cell lines (as determined by flow cytometry, PCR, and Western blot), as well as cell lines derived from other solid tumors. Normal B cells do not express FoxP3; however, expression could be induced after transformation with EBV in vitro and in vivo, suggesting that malignant transformation of healthy cells can induce FoxP3. In addition, a FOXP3 mRNA variant lacking exons 3 and 4 was identified in tumor cell lines but was absent from Treg. Interestingly, this alternative splicing event introduces a translation frame-shift that is predicted to encode a novel protein. Together, our results show that FoxP3, a key regulator of immune suppression, is not only expressed by Treg but also by melanoma cells, EBV-transformed B cells, and a wide variety of tumor cell lines.
authors.affiliation: Ludwig Institute for Cancer Research (Melbourne Center for Clinical Sciences), Austin Health, Heidelberg, Victoria, Australia. lisa.ebert@ludwig.edu.au
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ebert
authors.forename: Bee Shin
authors.initials: BS
authors.lastname: Tan
authors.forename: Judy
authors.initials: J
authors.lastname: Browning
authors.forename: Suzanne
authors.initials: S
authors.lastname: Svobodova
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Russell
authors.forename: Naomi
authors.initials: N
authors.lastname: Kirkpatrick
authors.forename: Craig
authors.initials: C
authors.lastname: Gedye
authors.forename: Denis
authors.initials: D
authors.lastname: Moss
authors.forename: Sweet Ping
authors.initials: SP
authors.lastname: Ng
authors.forename: Duncan
authors.initials: D
authors.lastname: MacGregor
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics* / Q000276:immunology; D005910:Glioma / Q000235:genetics / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000276:immunology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors