Premium
Pin1 acts as a modulator of cell proliferation through alteration in NF‐κB but not β‐catenin/TCF4 signalling in a subset of endometrial carcinoma cells
Author(s) -
Saegusa Makoto,
Hashimura Miki,
Kuwata Takeshi
Publication year - 2010
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2773
Subject(s) - transactivation , pin1 , cyclin d1 , cell cycle , cancer research , biology , catenin , cell growth , nf κb , beta catenin , e2f1 , microbiology and biotechnology , signal transduction , transcription factor , cell , wnt signaling pathway , gene , genetics , isomerase
Prolyl isomerase Pin1 is frequently up‐regulated in a variety of human malignancies, modulating signalling in several oncogenic pathways, including those involving NF‐κB and β‐catenin. Our previous study provided evidence that alterations in these signal pathways are essential events during trans ‐differentiation of endometrial carcinoma (Em Ca) cells. Here we focused on the functional roles of Pin1. In normal endometrium, Pin1 expression showed a stepwise decrease from proliferative to secretory phases during the menstrual cycle, correlating positively with cell proliferation and expression of several cell cycle‐related molecules including E2F1 and pRb. Transfection of E2F1 caused transactivation of Pin1 , indicating control by E2F1/Rb pathways. In Em Cas with morules, Pin1 expression was found to be significantly increased in glandular but not in morular components, correlating inversely with nuclear accumulation of β‐catenin. Overexpression also caused an increase in the stability of nuclear p65, leading to enhancement of NF‐κB‐mediated transactivation of the cyclin D1 gene, in contrast to minimal inhibition of β‐catenin/TCF4 transcription activity. These findings indicate that Pin1 may play an important role in preserving cell proliferative activity in glandular carcinoma components through enhancement of NF‐κB signalling, but its down‐regulation may be a key signal for induction of trans ‐differentiation of Em Ca cells, contributing to a shift from NF‐κB to β‐catenin/TCF signalling pathways. Copyright © 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.