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

Bee Shin Tan; Matthew R Anaka; Siddhartha Deb; Claudia Freyer; Lisa M Ebert; Anderly C Chueh; Sheren Al-Obaidi; Andreas Behren; Aparna Jayachandran; Jonathan Cebon; Weisan Chen; John M Mariadason

doi:10.18632/oncotarget.1600

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Research Papers:

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

Bee Shin Tan, Matthew R Anaka, Siddhartha Deb, Claudia Freyer, Lisa M Ebert, Anderly C Chueh, Sheren Al-Obaidi, Andreas Behren, Aparna Jayachandran, Jonathan Cebon, Weisan Chen and John M Mariadason _

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Oncotarget. 2014; 5:264-276. https://doi.org/10.18632/oncotarget.1600

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Abstract

BeeShin Tan1, Matthew Anaka1, Siddhartha Deb2, Claudia Freyer1, Lisa M. Ebert3, Anderly C. Chueh1, Sheren Al-Obaidi1, Andreas Behren1, Aparna Jayachandran1, Jonathan Cebon1, Weisan Chen4 and John M. Mariadason1

1 Ludwig Institute for Cancer Research Ltd. Melbourne-Austin Branch, Heidelberg, Victoria, Australia.

2 Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

3 Centre for Cancer Biology, SA Pathology, Frome Road, Adelaide, Australia.

4 School of Molecular Science, LaTrobe University, Bundoora, Victoria, Australia.

Correspondence:

John M. Mariadason, email:

Weisan Chen, email:

Keywords: FOXP3, melanoma, proliferation, apoptosis

Received: November 12, 2013 Accepted: December 20, 2013 Published: December 20, 2013

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.

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Research Papers:

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

Abstract