Up-regulation of Foxp3 inhibits cell proliferation, migration and invasion in epithelial ovarian cancer.

Abstract:

:The transcription factor Forkhead Box P3 (Foxp3) has been shown to play important roles in the occurring of regulatory T cells (Tregs). Limited evidence indicated that it was also expressed in tissues other than thymus and spleen, while, very recently, it was identified as a suppressor gene in breast cancer. However, the precise role and molecular mechanism of the action of Foxp3 in ovarian cancer remained unclear. To elucidate the function of Foxp3, we examined the expression of Foxp3 in ovarian cancerous cells and the consequences of up-regulation of Foxp3 in epithelial ovarian cancer cell lines, respectively. By multiple cellular and molecular approaches such as gene transfection, CCK-8 assay, flow cytometry, RT-PCR, in-cell western, wound healing assay, and invasion assay, we found that Foxp3 was weakly/no expressed in ovarian cancerous cells. Up-regulation of Foxp3 inhibited cell proliferation, decreased cell migration, and reduced cell invasion. Compared with control, Foxp3 up-regulated cells showed decreased expression of Ki-67 and cyclin-dependent kinases (CDKs). Moreover, up-regulation of Foxp3 reduced the expression of matrix metalloproteinase-2 (MMP-2) and urokinase-type plasminogen activator (uPA), resulting in the inhibition of cell migration and invasion. In addition, Foxp3 up-regulation inhibited the activation of mammalian target of rapamycin (mTOR) and NF-kappaB signaling. These findings suggested that up-regulation of Foxp3 could be a novel approach for inhibiting ovarian cancer progression.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Zhang HY,Sun H

doi

10.1016/j.canlet.2009.06.001

subject

Has Abstract

pub_date

2010-01-01 00:00:00

pages

91-7

issue

1

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(09)00405-4

journal_volume

287

pub_type

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