Effect of the modulation of leucine zipper tumor suppressor 2 expression on proliferation of various cancer cells functions as a tumor suppressor

• Published in: Molecular and cellular biochemistry 2011, Vol.346 (1-2), p.125-136
• Main Authors: Kim, Jong Myung, Song, Ji Sun, Cho, Hyun Hwa, Shin, Keun Koo, Bae, Yong Chan, Lee, Byung Ju, Jung, Jin Sup
• Format: Article
• Language: English
• Subjects: Amino acids; Base Sequence; beta Catenin - metabolism; Biochemistry; Biomedical and Life Sciences; Cancer; Cancer cells; Carcinogenesis; Cardiology; Cell growth; Cell Line, Tumor; Cell Proliferation; DNA binding proteins; DNA Primers; Embryonic development; Embryonic growth stage; Gene expression; Genes, Reporter; Genes, Tumor Suppressor; Humans; Leucine Zippers - genetics; Life Sciences; Medical Biochemistry; Muscle proteins; NF-kappa B - metabolism; Oncology; Prostate cancer; Proteins; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Stem cells; Tumors
• ISSN: 0300-8177; 1573-4919
• DOI: 10.1007/s11010-010-0599-y

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.