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TGF‐β induces novel Lef‐1 splice variants through a Smad‐independent signaling pathway
Author(s) -
Cordray Pauline,
Satterwhite Daniel J.
Publication year - 2005
Publication title -
developmental dynamics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.634
H-Index - 141
eISSN - 1097-0177
pISSN - 1058-8388
DOI - 10.1002/dvdy.20275
Subject(s) - wnt signaling pathway , biology , smad , enhancer , transforming growth factor beta , transcription factor , signal transduction , smad2 protein , transforming growth factor , r smad , beta catenin , microbiology and biotechnology , cancer research , growth factor , tgf alpha , gene , receptor , genetics
The lymphoid enhancer‐binding factor (Lef‐1) transcription factor is best known for the ability to transduce Wnt signals during development and to mediate excessive Wnt signaling in certain types of cancer. We recently identified and characterized a novel Wnt‐like effect of transforming growth factor‐beta (TGF‐β) on β‐catenin, the binding partner of Lef‐1. Therefore, we sought to determine the effect of TGF‐β on expression of the Lef/T‐cell–specific transcription factor (TCF) components of the Wnt pathway. We found that TGF‐β markedly induced Lef‐1 mRNA expression in cell lines originating from fetal lung (Mv1Lu) and newborn skin (Balb/MK), tissues that normally express Lef‐1 during development. Lef‐1 induction was temporally related to but independent of TGF‐β–induced G1 cell cycle arrest. Furthermore, the induction of Lef‐1 was independent of both new protein synthesis and Smad‐mediated signaling. Using TGF‐β–treated Mv1Lu cells, we identified multiple splice forms of Lef‐1, including novel variants that lack both exons 2 and 3. We conclude that the induction of Lef‐1 has permissive effects on the well‐characterized TGF‐β signal that inhibits c‐ myc expression and induces a G1 arrest. Developmental Dynamics 232:969–978, 2005. © 2005 Wiley‐Liss, Inc.