Apoptosis, proliferation and p12doc-1 profiles in normal, dysplastic and malignant squamous epithelium of the Syrian hamster cheek pouch model

Kohno, Yohko; Patel, Vipul; Kim, Yong; Tsuji, Takanori; Chin, Byung-Rho; Sun, Moyi; Bruce Donoff, R; Kent, Ralph; Wong, David; Todd, Randy

« Previous Next »Oral Oncology
Volume 38, Issue 3 , Pages 274-280, April 2002

Apoptosis, proliferation and p12^doc-1 profiles in normal, dysplastic and malignant squamous epithelium of the Syrian hamster cheek pouch model

Yohko Kohno
- Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA
Vipul Patel
- Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA
Yong Kim
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, 1 Fruit Street, Boston, MA 02114, USA
Takanori Tsuji
- Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA
Byung-Rho Chin
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, 1 Fruit Street, Boston, MA 02114, USA
Moyi Sun
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, 1 Fruit Street, Boston, MA 02114, USA
R Bruce Donoff
- Dean, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA
Ralph Kent
- Forsyth Institute, Boston, MA 02115, USA
David Wong
- Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, 188 Longwood Avenue, Boston, MA 02115, USA
Randy Todd
- Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, 1 Fruit Street, Boston, MA 02114, USA
- Corresponding author. Present address. Department of Oral & Maxillofacial Surgery, Harvard School of Dental Medicine/Massachusetts General Hospital, 188 Longwood Avenue, Boston, MA 02115, USA. Fax: +1-617-432-2449

Received 25 April 2001; accepted 18 May 2001.

Abstract

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.

Keywords: Apoptosis, Proliferation, doc-1, Oral cancer, Syrian hamster cheek pouch carcinoma model