Gene expression analysis of human middle ear cholesteatoma using complementary DNA arrays.
OBJECTIVE
To identify genes regulated in human cholesteatoma compared with normal skin tissue using complementary DNA arrays.


METHODS
In vitro analysis.


METHODS
Eight cholesteatoma and retroauricular skin samples were obtained from the same patients during surgery. Upregulated and downregulated genes were highlighted using complementary DNA arrays for screening. Reverse transcriptase-polymerase chain reaction and immunohistochemical staining were performed to confirm the results of the complementary DNA array.


RESULTS
Twelve genes were found to be induced or upregulated in cholesteatoma compared with skin samples. These included genes involved in cell proliferation and differentiation (eg, calgranulin A, calgranulin B, psoriasin, thymosin beta-10) and cell invasion (eg, cathepsin C, cathepsin D, cathepsin H). Analyses by means of reverse transcription-polymerase chain reaction showed enhanced expression of several genes including calgranulin A, calgranulin B, psoriasin, thymosin beta-10, cathepsin C, cathepsin D, and cathepsin H in cholesteatoma, supporting the findings from the gene array. In addition, it was verified by immunohistochemical analysis that the expressions of Calgranulin A, Calgranulin B, and Cathepsin D were mainly located in cholesteatoma epithelium.


CONCLUSIONS
The observed alteration in gene expression may play a role in various mechanisms of pathogenesis in cholesteatoma.
Tokuriki
Masaharu
M
Department of Otolaryngology, Fukui Medical University, Matsuoka, Japan.
Noda
Ichiro
I
Saito
Takehisa
T
Narita
Norihiko
N
Sunaga
Hiroshi
H
Tsuzuki
Hideaki
H
Ohtsubo
Toshio
T
Fujieda
Shigeharu
S
Saito
Hitoshi
H
D000199:Actins / Q000235:genetics; D000906:Antibodies / Q000276:immunology; D002135:Calcium-Binding Proteins / Q000235:genetics; D040501:Calgranulin A / Q000235:genetics; D040502:Calgranulin B / Q000235:genetics; D020789:Cathepsin C / Q000235:genetics; D002402:Cathepsin D / Q000235:genetics; D056655:Cathepsin H; D002403:Cathepsins / Q000235:genetics; D002454:Cell Differentiation; D002465:Cell Movement; D018424:Cholesteatoma, Middle Ear / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003546:Cysteine Endopeptidases / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics*; D015536:Down-Regulation; D015870:Gene Expression / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; D013947:Thymosin / Q000235:genetics; D015854:Up-Regulation
D000199:Actins; D000906:Antibodies; D002135:Calcium-Binding Proteins; D040501:Calgranulin A; D040502:Calgranulin B; D017931:DNA Primers; D018076:DNA, Complementary; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D013947:Thymosin; C039302:thymosin beta(10); D002403:Cathepsins; D020789:Cathepsin C; D003546:Cysteine Endopeptidases; C534126:CTSH protein, human; D056655:Cathepsin H; D002402:Cathepsin D