Effect of the modulation of leucine zipper tumor suppressor 2 expression on proliferation of various cancer cells functions as a tumor suppressor.
β-catenin is a component of the adhesion complex linking cadherin and actin cytoskeleton, as well as a major mediator of the Wnt pathway, which is a critical signal cascade regulating embryonic development, cell polarity, carcinogenesis, and stem cell function. NF-κB functions as a key regulator of immune responses and apoptosis, and mutations in NF-κB signaling can lead to immune diseases and cancers. We previously showed that NF-κB-mediated modulation of β-catenin/Tcf signaling is mediated by leucine zipper tumor suppressor 2 (Lzts2) and that lzts2 expression is differentially regulated in various cancer cells. Its functional significances, however, are poorly understood. We showed that NF-κB-induced modulation of β-catenin/Tcf pathway is regulated by lzts2 expression in mesenchymal stem cells (MSCs) and several cancer cells, and that NF-κB-induced lzts2 expression is differentially regulated among cancer cell types. Here, using a promoter-reporter assay and EMSA, we demonstrate that NF-κB regulates lzts2 transcription by directly binding to the lzts2 promoter, and that NF-κB-induced lzts2 transcription differs by cell types. Modulation of lzts2 expression by lentiviral techniques affected proliferation and tumorigenicity of several cancer cell lines such as breast, colon, prostate cancer, and glioma, but did not affect cisplatin sensitivity or cell migration. Our data indicate that lzts2 expression is transcriptionally regulated by NF-κB activities, and the modulation of lzts2 expression affects cell proliferation and tumor growth through the Wnt/β-catenin pathway in various cancer cell lines.
Kim
Jong Myung
JM
MD-PhD Program, School of Medicine, Pusan National University, Yangsan, Korea.
Song
Ji Sun
JS
Cho
Hyun Hwa
HH
Shin
Keun Koo
KK
Bae
Yong Chan
YC
Lee
Byung Ju
BJ
Jung
Jin Sup
JS
D001483:Base Sequence; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006801:Humans; D016350:Leucine Zippers / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism
D017931:DNA Primers; D016328:NF-kappa B; D051176:beta Catenin