Role of Bcl-xL protein in differentiation and apoptosis of human middle ear cholesteatoma epithelium.
OBJECTIVE
To compare the mechanisms of proliferation, differentiation, and apoptosis in middle ear cholesteatoma epithelium with those of normal external ear canal epithelium.


METHODS
The localizations of the expression of Bcl-xL protein and involucrin and the presence of apoptotic cells were determined for tissue slices of middle ear cholesteatoma epithelium and compared with the findings for normal external ear canal epithelium. In addition, SCC-25/bcl-xL transfectants showing the overexpression of Bcl-xL were used to investigate the effect of this protein on the expression of involucrin, which is a marker of epithelial cell differentiation.


METHODS
Cholesteatoma tissue specimens were surgically excised from 10 patients. Normal skin specimens collected from the external ear canal of the 10 patients were used as control specimens.


RESULTS
The expression of Bcl-xL was detected in the vicinity of the basal cell layer of both the cholesteatoma epithelium and the normal external ear canal epithelium. Conversely, the expression of involucrin (ie, a marker of epithelial cell differentiation) increased in proportion to the shallowness of the epithelial layer. In situ labeling detected apoptotic cells in the spinous and granular cell layers of cholesteatoma tissue sections and similar findings in the normal external skin specimens. Western blot analysis confirmed that the expression of involucrin protein was the same in both wild-type SCC-25 cells and the SCC-25/bcl-xL transfectants.


CONCLUSIONS
In both the cholesteatoma epithelium and the normal external ear canal epithelium, differentiation and apoptosis begin when the epithelial cells separate from the basal cells. The mechanisms behind these changes, at least in apoptosis, appear to be controlled by the expression of the Bcl-xL protein.
Kojima
H
H
Department of Otorhinolaryngology, Jikei University School of Medicine, Tokyo, Japan.
Miyazaki
H
H
Tanaka
Y
Y
Shiwa
M
M
Koga
T
T
Moriyama
H
H
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D002455:Cell Division / Q000235:genetics; D018424:Cholesteatoma, Middle Ear / Q000235:genetics* / Q000473:pathology; D004424:Ear Canal / Q000473:pathology; D004432:Ear, Middle / Q000473:pathology; D004848:Epithelium / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011498:Protein Precursors / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D012016:Reference Values; D012867:Skin / Q000473:pathology; D014162:Transfection / Q000235:genetics; D014407:Tumor Cells, Cultured; D051020:bcl-X Protein
C494811:BCL2L1 protein, human; D011498:Protein Precursors; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein; C032253:involucrin