TY - JOUR
T1 - Peroxisome proliferator-activated receptor β/δ expression and activation in lung cancer
AU - Pedchenko, Tetyana V.
AU - Gonzalez, Adriana L.
AU - Wang, Ding Zhi
AU - DuBois, Raymond N.
AU - Massion, Pierre P.
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2008/12/1
Y1 - 2008/12/1
N2 - Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ligand-binding inducible transcriptional factor linked to carcinogenesis. Important functions of PPARβ/δ were demonstrated in series of human epithelial cancers; however, its role in lung cancer remains controversial. We investigated the differential expression level and localization of PPARβ/δ in tumors and adjacent normal lung tissue, and the effect of PPARβ/δ activation on lung cancer cell proliferation and apoptosis. PPARβ/δ was expressed in all studied human non-small cell lung cancers, and strong PPARβ/δ immunoreactivity was observed in epithelial cells of more than 75% of studied lung tumors. PPARβ/δ expression was consistently limited to the cancer cells in tumor tissue, while in adjacent normal lung tissue it was limited predominantly to the mononuclear cells. We found that ligand-binding activation of PPARβ/δ stimulates cell proliferation (an effect that was blocked by a dominant-negative construct of PPARβ/δ), stimulates anchorage-independent cell growth, and inhibits apoptosis in lung cancer cell lines. Importantly, the activation of PPARβ/δ induces Akt phosphorylation correlated with up-regulation of PDK1, down-regulation of PTEN, and increased expression of Bcl-xL and COX-2. These findings indicate that PPARβ/δ exerts proliferative and anti-apoptotic effects via PI3K/Akt1 and COX-2 pathways. In conclusion, PPARβ/δ is strongly expressed in the majority of lung cancers, and its activation induces proliferative and survival response in non-small cell lung cancer.
AB - Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) is a ligand-binding inducible transcriptional factor linked to carcinogenesis. Important functions of PPARβ/δ were demonstrated in series of human epithelial cancers; however, its role in lung cancer remains controversial. We investigated the differential expression level and localization of PPARβ/δ in tumors and adjacent normal lung tissue, and the effect of PPARβ/δ activation on lung cancer cell proliferation and apoptosis. PPARβ/δ was expressed in all studied human non-small cell lung cancers, and strong PPARβ/δ immunoreactivity was observed in epithelial cells of more than 75% of studied lung tumors. PPARβ/δ expression was consistently limited to the cancer cells in tumor tissue, while in adjacent normal lung tissue it was limited predominantly to the mononuclear cells. We found that ligand-binding activation of PPARβ/δ stimulates cell proliferation (an effect that was blocked by a dominant-negative construct of PPARβ/δ), stimulates anchorage-independent cell growth, and inhibits apoptosis in lung cancer cell lines. Importantly, the activation of PPARβ/δ induces Akt phosphorylation correlated with up-regulation of PDK1, down-regulation of PTEN, and increased expression of Bcl-xL and COX-2. These findings indicate that PPARβ/δ exerts proliferative and anti-apoptotic effects via PI3K/Akt1 and COX-2 pathways. In conclusion, PPARβ/δ is strongly expressed in the majority of lung cancers, and its activation induces proliferative and survival response in non-small cell lung cancer.
KW - Apoptosis
KW - Non-small cell lung cancer
KW - PPARβ/δ
KW - Proliferation
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U2 - 10.1165/rcmb.2007-0426OC
DO - 10.1165/rcmb.2007-0426OC
M3 - Article
C2 - 18566335
AN - SCOPUS:56049083203
VL - 39
SP - 689
EP - 696
JO - American Journal of Respiratory Cell and Molecular Biology
JF - American Journal of Respiratory Cell and Molecular Biology
SN - 1044-1549
IS - 6
ER -