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Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB.
Soh, Hendrick; Venkatesan, Natarajan; Veena, Mysore S; Ravichandran, Sandhiya; Zinabadi, Alborz; Basak, Saroj K; Parvatiyar, Kislay; Srivastava, Meera; Liang, Li-Jung; Gjertson, David W; Torres, Jorge Z; Moatamed, Neda A; Srivatsan, Eri S.
Afiliación
  • Soh H; Division of General Surgery, Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Venkatesan N; Division of General Surgery, Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Veena MS; Department of Medicine, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Ravichandran S; Division of General Surgery, Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Zinabadi A; Division of General Surgery, Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Basak SK; Department of Medicine, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Parvatiyar K; Department of Microbiology, Immunology and Molecular Genetics, UCLA, Los Angeles, California, USA.
  • Srivastava M; Department of Anatomy, Physiology and Genetics and Institute of Molecular Medicine, Uniformed Services University of Health Services School of Medicine, Bethesda, Maryland, USA.
  • Liang LJ; Department of Medicine, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Gjertson DW; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Torres JZ; Department of Chemistry and Biochemistry, UCLA, Los Angeles, California, USA.
  • Moatamed NA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
  • Srivatsan ES; Division of General Surgery, Department of Surgery, VAGLAHS/David Geffen School of Medicine at UCLA, Los Angeles, California, USA Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California, USA esrivats@g.ucla.edu.
Mol Cell Biol ; 36(12): 1776-92, 2016 06 15.
Article en En | MEDLINE | ID: mdl-27090639
We and others have shown that the cystatin E/M gene is inactivated in primary human tumors, pointing to its role as a tumor suppressor gene. However, the molecular mechanism of tumor suppression is not yet understood. Using plasmid-directed cystatin E/M gene overexpression, a lentivirus-mediated tetracycline-inducible vector system, and human papillomavirus 16 (HPV 16) E6 and E7 gene-immortalized normal human epidermal keratinocytes, we demonstrated intracellular and non-cell-autonomous apoptotic growth inhibition of tumor cell lines and that growth inhibition is associated with cytoplasmic retention of NF-κB. We further demonstrated decreased phosphorylation of IκB kinase (IKKß) and IκBα in the presence of tumor necrosis factor alpha (TNF-α), confirming the role of cystatin E/M in the regulation of the NF-κB signaling pathway. Growth suppression of nude mouse xenograft tumors carrying a tetracycline-inducible vector system was observed with the addition of doxycycline in drinking water, confirming that the cystatin E/M gene is a tumor suppressor gene. Finally, immunohistochemical analyses of cervical carcinoma in situ and primary tumors have shown a statistically significant inverse relationship between the expression of cystatin E/M and cathepsin L and a direct relationship between the loss of cystatin E/M expression and nuclear expression of NF-κB. We therefore propose that the cystatin E/M suppressor gene plays an important role in the regulation of NF-κB.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Cuello Uterino / FN-kappa B / Factor de Necrosis Tumoral alfa / Proteínas I-kappa B / Citoplasma / Cistatina M Límite: Animals / Female / Humans Idioma: En Revista: Mol Cell Biol Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Cuello Uterino / FN-kappa B / Factor de Necrosis Tumoral alfa / Proteínas I-kappa B / Citoplasma / Cistatina M Límite: Animals / Female / Humans Idioma: En Revista: Mol Cell Biol Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos