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PMID: 24406338 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

FOXP3 over-expression inhibits melanoma tumorigenesis via effects on proliferation and apoptosis.

Oncotarget ·Vol. 5 ·No. 1 ·2014-01-15 ·Pages 264-76

Tan B, Anaka M, Deb S, Freyer C, Ebert LM, Chueh AC, Al-Obaidi S, Behren A, Jayachandran A, Cebon J, Chen W, Mariadason JM

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.

MeSH Terms
Animals Apoptosis/physiology Carcinogenesis Cell Growth Processes/physiology Cell Line, Tumor Forkhead Transcription Factors/biosynthesis,genetics Humans Melanoma/genetics,metabolism,pathology Mice Mice, Inbred BALB C Mice, Nude Neoplasm Metastasis Transfection
Chemicals
FOXP3 protein, human Forkhead Transcription Factors
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Tan BeeShin
Ludwig Institute for Cancer Research Ltd. Melbourne-Austin Branch, Heidelberg, Victoria, Australia.
Anaka Matthew
Deb Siddhartha
Freyer Claudia
Ebert Lisa M
Chueh Anderly C
Al-Obaidi Sheren
Behren Andreas
Jayachandran Aparna
Cebon Jonathan
Chen Weisan
Mariadason John M
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Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
DOI
10.18632/oncotarget.1600
Published
2014-01-15
Pages
264-76
Language
English
Region
United States
NLM ID
101532965
PMCID
PMC3960207
Subset
IM
External Links
PubMed source DOI: 10.18632/oncotarget.1600 PMC Full Text View journal details
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