title: Aberrant expression of epidermal growth factor receptor and its interaction with protein kinase C δ in inflammation associated neoplastic transformation of human esophageal epithelium in high risk populations.
abstract: OBJECTIVE
  Esophageal cancer is the second most common cancer among Indian males and is mostly associated with tobacco smoking and alcohol consumption. Epidermal growth factor receptor (EGFR) is a member of Type I tyrosine kinases. Its activation causes the docking of various proteins in its cytosolic tail. In the present study we have analyzed the expression pattern of EGFR, protein kinase C δ (PKCδ), tumor necrosis factor-α (TNF-α), nuclear factor κB (NFκB) and the interactions between EGFR and PKCδ in various pathological conditions.
  
  
  METHODS
  Human esophageal biopsies were obtained from 93 patients with a past history of smoking and alcohol consumption: 20 showed normal mucosa, 40 with dysplasia and 33 squamous cell carcinoma (SCC). These pathological conditions were analyzed immunohistochemically for the presence of EGFR expression and then subsequently analyzed using immunoblot and immunoprecipitation.
  
  
  RESULTS
  A statistically significant difference of EGFR overexpression was found between low- and high-grade dysplasia and carcinoma (χ² = 3.3, χ² = 3.42: P = 0.07, 0.33). A statistical significance was observed between dysplasia and SCC and in all histopathological types (χ² = 4, χ² = 4.9; P < 0.05, P = 0.18 and χ² = 26.3, 26.6; P < 0.001). EGFR tyrosine phosphorylation and its association with PKCδ was significantly higher in all histopathological types with χ² = 7.965; P < 0.05 and 4.0830; P = 0.2530.
  
  
  CONCLUSIONS
  Altogether, our findings reveal that the activation of EGFR and its subsequent interaction with PKCδ under inflammatory conditions might positively be attributed to the transformation of normal esophageal epithelia to SCC, which could explain ongoing inflammation in normal mucosa in a population prone to smoking and alcoholism.
authors.affiliation: Department of Zoology, Unit of Biochemistry, University of Madras, Guindy Campus, India.
authors.forename: Seshacharyulu
authors.initials: S
authors.lastname: Parthasarathy
authors.forename: Devaraj
authors.initials: D
authors.lastname: Dhayaparan
authors.forename: Venkatraman
authors.initials: V
authors.lastname: Jayanthi
authors.forename: Sivasitambaram Niranjali
authors.initials: SN
authors.lastname: Devaraj
authors.forename: Halagowder
authors.initials: H
authors.lastname: Devaraj
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000009:adverse effects; D001706:Biopsy; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology; D016009:Chi-Square Distribution; D066246:ErbB Receptors / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D004941:Esophagitis / Q000201:enzymology* / Q000473:pathology; D004947:Esophagus / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007194:India; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000032:analysis; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis; D016328:NF-kappa B / Q000032:analysis; D009367:Neoplasm Staging; D010766:Phosphorylation; D011230:Precancerous Conditions / Q000201:enzymology* / Q000473:pathology; D051745:Protein Kinase C-delta / Q000032:analysis*; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C512478:EGFR protein, human; D066246:ErbB Receptors; C497258:PRKCD protein, human; D051745:Protein Kinase C-delta; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases