title: Downregulation of cornulin in esophageal squamous cell carcinoma.
abstract: Early events in the development of esophageal squamous cell carcinoma (ESCC) are poorly understood and many of the key molecules involved have not yet been identified. We previously used isobaric tags for a relative and absolute quantitation (iTRAQ)-based quantitative proteomics approach to identify differentially expressed proteins in ESCC tissue as compared to the adjacent normal mucosa. Cornulin was identified as one of the major downregulated molecules in ESCC. Cornulin is a member of the S100 fused-type protein family, which has an EF-hand calcium binding motif and multiple tandem repeats of specific peptide motifs. Cornulin was 5-fold downregulated in ESCC as compared to normal epithelium mirroring our previous findings in a gene expression study of ESCC. In the present study, we performed immunohistochemical validation of cornulin (CRNN) in a larger set of patients with ESCC. Downregulation of cornulin was observed in 89% (n=239) of 266 different ESCC tissues arrayed on tissue microarrays (TMAs). Expression of cornulin was observed in the prickle and functional cell layers of normal esophageal mucosa, localized predominantly in the cytoplasm and perinuclear region. The large majority of ESCC cases had little or no expression of cornulin in the carcinoma or stroma. These findings suggest that cornulin is an important molecule in normal esophageal pathology and is likely lost during the conversion of normal to neoplastic epithelium.
authors.affiliation: Institute of Bioinformatics, International Technology Park, Bangalore 560066, India.
authors.forename: Harsh
authors.initials: H
authors.lastname: Pawar
authors.forename: Jagadeesha
authors.initials: J
authors.lastname: Maharudraiah
authors.forename: Manoj Kumar
authors.initials: MK
authors.lastname: Kashyap
authors.forename: Jyoti
authors.initials: J
authors.lastname: Sharma
authors.forename: Srinivas Manda
authors.initials: SM
authors.lastname: Srikanth
authors.forename: Robin
authors.initials: R
authors.lastname: Choudhary
authors.forename: Sandip
authors.initials: S
authors.lastname: Chavan
authors.forename: Gajanan
authors.initials: G
authors.lastname: Sathe
authors.forename: Hosuru Chikkalingaiah
authors.initials: HC
authors.lastname: Manju
authors.forename: Kariyanakatte Veeraiah Veerendra
authors.initials: KV
authors.lastname: Kumar
authors.forename: Manavalan
authors.initials: M
authors.lastname: Vijayakumar
authors.forename: Ravi
authors.initials: R
authors.lastname: Sirdeshmukh
authors.forename: Hindahally Chandregowda
authors.initials: HC
authors.lastname: Harsha
authors.forename: Thottethodi Subrahmanya Keshava
authors.initials: TS
authors.lastname: Prasad
authors.forename: Akhilesh
authors.initials: A
authors.lastname: Pandey
authors.forename: Rekha Vijay
authors.initials: RV
authors.lastname: Kumar
mesh_terms: D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015536:Down-Regulation; D004938:Esophageal Neoplasms / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009418:S100 Proteins / Q000378:metabolism
chemical_list: C418764:CRNN protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009418:S100 Proteins