title: Expression of vascular endothelial growth factor and transcription factors HIF-1, NF-kB expression in squamous cell carcinoma of head and neck; association with proteasome and calpain activities.
abstract: BACKGROUND
  The transcription factors NF-kB, HIF-1 and vascular endothelial growth factors (VEGF) are known to play an important role in pathogenesis of squamous cell carcinoma of head and neck (SCCHN).
  
  
  OBJECTIVE
  The aim of the study was to determine the NF-kB, HIF-1 and VEGF, expression their characteristics in squamous cell carcinoma of head and neck.
  
  
  METHODS
  Transcription factors and VEGF expression were measured by ELISA kits. Proteasome and calpain activity were determined using specific fluorogenic substrate. Proteasome subunits composition was measured by Western blot analysis.
  
  
  RESULTS
  In the present study, we revealed the connection between SCCHN lymphogenous metastasis development and NF-kB p50 expression. An increase in total, 26S and 20S proteasome activities and calpain activity was observed in cancer tissues in comparison with agreed standard (non-transformed tissue). The dynamics of changes in proteasome activity and proteasome subunits content during lymph nodes metastasis development had a complex pattern. Nonparametric analysis of variance showed the connection between the extent of metastatic affection of regional lymph nodes, total proteasome activity and LMP2 expression. Proteasome and calpain systems corresponded and interacted with each other. We also revealed a positive correlation between the NF-kB p65 and p50 expression and proteasome activity.
  
  
  CONCLUSIONS
  Taken together, our results suggest that above mentioned transcription factors and intracellular proteolytic systems are involved in SCCHN progression and metastasis. Moreover, the opportunity of transcription factors regulation by proteasome takes place in oncogenesis of SCCHN. The results provide a basis for new prognostic tests and development of novel targeted therapy.
authors.affiliation: Cancer Research Institute, Siberian Branch of Russian Academy of Medical Sciences, Tomsk, Russian Federation. SpirinaLV@oncology.tomsk.ru
authors.forename: Liudmila V
authors.initials: LV
authors.lastname: Spirina
authors.forename: Irina V
authors.initials: IV
authors.lastname: Kondakova
authors.forename: Evgeny L
authors.initials: EL
authors.lastname: Choynzonov
authors.forename: Svetlana Y
authors.initials: SY
authors.lastname: Chigevskaya
authors.forename: Dmitry A
authors.initials: DA
authors.lastname: Shishkin
authors.forename: Denis Y
authors.initials: DY
authors.lastname: Kulbakin
mesh_terms: D015153:Blotting, Western; D002154:Calpain / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006258:Head and Neck Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D011379:Prognosis; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002154:Calpain; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease