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Disruption of transforming growth factor-beta signaling through beta-spectrin ELF leads to hepatocellular cancer through cyclin D1 activation.
Kitisin, K; Ganesan, N; Tang, Y; Jogunoori, W; Volpe, E A; Kim, S S; Katuri, V; Kallakury, B; Pishvaian, M; Albanese, C; Mendelson, J; Zasloff, M; Rashid, A; Fishbein, T; Evans, S R T; Sidawy, A; Reddy, E P; Mishra, B; Johnson, L B; Shetty, K; Mishra, L.
Afiliación
  • Kitisin K; Department of Surgical Sciences, School of Medicine, Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA.
Oncogene ; 26(50): 7103-10, 2007 Nov 01.
Article en En | MEDLINE | ID: mdl-17546056
Transforming growth factor-beta (TGF-beta) signaling members, TGF-beta receptor type II (TBRII), Smad2, Smad4 and Smad adaptor, embryonic liver fodrin (ELF), are prominent tumor suppressors in gastrointestinal cancers. Here, we show that 40% of elf(+/-) mice spontaneously develop hepatocellular cancer (HCC) with markedly increased cyclin D1, cyclin-dependent kinase 4 (Cdk4), c-Myc and MDM2 expression. Reduced ELF but not TBRII, or Smad4 was observed in 8 of 9 human HCCs (P<0.017). ELF and TBRII are also markedly decreased in human HCC cell lines SNU-398 and SNU-475. Restoration of ELF and TBRII in SNU-398 cells markedly decreases cyclin D1 as well as hyperphosphorylated-retinoblastoma (hyperphosphorylated-pRb). Thus, we show that TGF-beta signaling and Smad adaptor ELF suppress human hepatocarcinogenesis, potentially through cyclin D1 deregulation. Loss of ELF could serve as a primary event in progression toward a fully transformed phenotype and could hold promise for new therapeutic approaches in human HCCs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Portadoras / Espectrina / Ciclinas / Carcinoma Hepatocelular / Factor de Crecimiento Transformador beta2 / Neoplasias Hepáticas Experimentales / Proteínas de Microfilamentos Límite: Animals / Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Portadoras / Espectrina / Ciclinas / Carcinoma Hepatocelular / Factor de Crecimiento Transformador beta2 / Neoplasias Hepáticas Experimentales / Proteínas de Microfilamentos Límite: Animals / Humans Idioma: En Revista: Oncogene Asunto de la revista: BIOLOGIA MOLECULAR / NEOPLASIAS Año: 2007 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido