1. ¹UCLA School of Dentistry, Los Angeles, CA 90095, USA
2. ²UCLA Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA
3. ³Evanston Northwestern Healthcare Research Institute, Feinberg School of Medicine, Northwestern University, Evanston, IL 60201, USA
4. ⁴David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA

Correspondence: Professor MK Kang, UCLA School of Dentistry, CHS 43-009, 10833 Le Conte Ave. Los Angeles, CA 90095-1668, USA. E-mail: mkang@dent.ucla.edu

Received 5 July 2006; Revised 2 November 2006; Accepted 14 November 2006; Published online 19 December 2006.

Abstract

Bmi-1 is a polycomb group protein that was identified as c-myc cooperating oncogene in murine lymphomagenesis. The current study was undertaken to determine the role of Bmi-1 in human oral carcinogenesis. Bmi-1 protein and RNA expression levels were markedly enhanced in the cells of oral squamous cell carcinomas (OSCC) compared with that of normal human oral keratinocytes (NHOK). Enhanced-Bmi-1 expression was also detected in situ in the archived oral mucosal tissues with cancerous and precancerous histopathology, including that of mild epithelial dysplasia. Thus, Bmi-1 expression occurs at a very early stage in oral carcinogenesis. To determine the biological role of Bmi-1 in cell proliferation, endogenous Bmi-1 was knocked down in actively proliferating SCC4 cells and NHOK by RNA interference. After Bmi-1 knockdown, cell replication was severely retarded. However, the expression of p16^INK4A, a known cellular target of Bmi-1, was not changed in cells with or without Bmi-1 knockdown. Furthermore, Bmi-1 knockdown in HOK-16B-BaP-T cells, in which the p16^INK4A/pRb pathway was abrogated, led to immediate arrest of replication and loss of viable cells. Thus, our data suggest that Bmi-1 may act through p16^INK4A-independent pathways to regulate cellular proliferation during oral cancer progression.