Apoptosis, proliferation and p12(doc-1) profiles in normal, dysplastic and malignant squamous epithelium of the Syrian hamster cheek pouch model.
Disruption of the homeostatic balance between proliferation and apoptosis is widely believed to contribute to human oral carcinogenesis. Using the Syrian hamster oral cancer model, we examined normal, hyperplastic, dysplastic and malignant oral epithelium for the fraction of apoptotic, proliferating and p12(doc-1) expressing keratinocytes using the TUNEL assay, as well as PCNA and p12(doc-1) immunostaining, respectively. The percentage of TUNEL positive cells progressively increased from normal to dysplastic epithelium (P<0.0019), but returned to normal keratinocyte levels in the malignant epithelium (P<0.20). However, PCNA positive cells increased progressively through hamster oral malignant progression (P<0.0012). The overall ratio of apoptotic to proliferating keratinocytes remains similar until the transition between dysplastic and malignant epithelium, where the ratio is markedly reduced (P<0.05). p12(doc-1) labeling demonstrated a similar expression pattern (P<0.008). This study demonstrates that apoptosis, proliferation and the expression of p12(doc-1) reflects alterations reported during human oral carcinogenesis and supports the use of the Syrian hamster model for the further examination of these pathways.
Kohno
Yohko
Y
Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, MA 02115, USA.
Patel
Vipul
V
Kim
Yong
Y
Tsuji
Takanori
T
Chin
Byung Rho
BR
Sun
Moyi
M
Bruce Donoff
R
R
Kent
Ralph
R
Wong
David
D
Todd
Randy
R
D000818:Animals; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D002610:Cheek; D006224:Cricetinae; D004848:Epithelium / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D020287:In Situ Nick-End Labeling; D008647:Mesocricetus; D008940:Mitotic Index; D023421:Models, Animal; D009062:Mouth Neoplasms / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D025521:Tumor Suppressor Proteins / Q000032:analysis
C096151:CDK2AP1 protein, human; D025521:Tumor Suppressor Proteins