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Tieg1/Klf10 is upregulated by NGF and attenuates cell cycle progression in the pheochromocytoma cell line PC12
Author(s) -
Spittau Gabriele,
Happel Nicole,
Behrendt Maik,
Chao T. Ivo,
Krieglstein Kerstin,
Spittau Björn
Publication year - 2010
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22364
Subject(s) - downregulation and upregulation , pheochromocytoma , cell cycle progression , nerve growth factor , cell culture , line (geometry) , microbiology and biotechnology , cell cycle , cell , neuroscience , chemistry , medicine , biology , biochemistry , genetics , receptor , gene , geometry , mathematics
Abstract The transcription factor Tieg1/Klf10 belongs to a family of Sp1/Klf proteins that have been shown to play important roles during development and maintenance of various tissues and cell types. Upregulation of Tieg1/Klf10 has been reported for TGF‐β, BMP2, BMP4, ActivinA and GDNF as members of the TGF‐β superfamily. Moreover, estrogen, the cytostatic drugs homoharringtonine and velcade as well as nitric oxide are also able to trigger Tieg1/Klf10 transcription. Recent studies suggest a role for members of the neurotrophin family in regulating Tieg1/Klf10 transcriptional upregulation. Using semi‐quantitative RT‐PCR and immunoblotting, we present data describing that nerve growth factor (NGF) regulates the expression of Tieg1/Klf10 in the pheochromocytoma cell line PC12 in a TrkA‐dependent manner. Moreover, we provide evidence for the existence of NGF‐responsive elements in the 5′‐regulatory region of Tieg1/Klf10 that contain binding sites for the transcription factors Sp1 and CREB. After treatment with NGF PC12 cells exit the cell cycle and start to differentiate towards a neuron‐like phenotype indicated by neurite outgrowth. Using flow cytometry and differentiation assays we demonstrate that Tieg1/Klf10 reduces cell cycle progression in PC12 cells but fails to promote their terminal differentiation. Together, our results identify Tieg1/Klf10 as a new NGF target gene and substantiate its anti‐proliferative function in the NGF signaling pathway in PC12 cells. © 2010 Wiley‐Liss, Inc.