Expression of Bcl-2 Gene Family in Leukoplakia and Squamous Cell Carcinoma of Oral Mucosa
Korean Journal of Oral and Maxillofacial Pathology (대한구강악안면병리학회지)
Korean Journal of Oral and Maxillofacial Pathology (대한구강악안면병리학회지), Vol.25(1) : 41~60, 2001
Oral mucosa is a useful model which enables us to observe the multi-stage carcinogenesis. Thus, it is meaningful to find out a biomarker which helps to evaluate the prognosis of oral premalignant lesions.
Apoptosis is a physiologic process which permits cell turnover and is critical for the maintenance of homeostasis in tissues. Bcl-2 is known to be key regulator of apoptosis and constitutes gene family of many structural homologues dividing into anti-apoptotic protein Bcl-2, Bcl-XL, Mcl-1 and pro-apoptotic protein Bax, Bcl-Xs, Bad, Bak. Two family members in particular, Bcl-2 and Bcl-XL function as potent inhibitors of apoptosis and have been implicated in a number of human cancer. However the relative expression of these family members in head and neck multistage carcinogenesis has been controversial.
In this study, 27 cases of leukoplakia, 36 squamous cell carcinomas and 5 normal mucosas were obtained from the files of the Department of Oral Pathology of the Dental Hospital of Yonsei University. The immunohistochemical staining and Western blot analysis with the paraffin sections and established oral cancer cell lines were performed using antibodies of Bcl-2, Bcl-XS/L, Bax.
The results were as follows : 1. Bcl-2 protein did not express in normal, leukoplakia and cancer tissue sections as well as the established cancer cell lines.
2. Bcl-XS/L protein was expressed in the cytoplasm of basal cell layer for normal mucosa and leukoplakia and also frequently appers in upper cell layer for severe dysplasia. Also overall up regulation of Bcl-XS/L protein was identified during the progress of carcinoma.
3. Immunostaining on the oral cancer cell lines with Bcl-XS/L resulted in expression of the protein in most of cancer cell lines. Especially it was markedly expressed at the perinuclear cytoplasm. Western blot analysis showed that normal cell express Bcl-Xs, while tumor cells express Bcl-XL.
4. The expression of Box protein was confined in prickle cell layer for normal mucosa and increases in prickle cell layer of leukoplakia showing hyperplasia. Neither immunohistochemical stain nor western blot analysis showed Bax expression in established oral cancer cell lines.
These observations suggest that Bcl-2 protein is not expressed in the development of oral squamous cell carcinoma, and Bax is believed to participate in the differentiation of oral keratinocyte. Bcl-XS/L expression was related to the progression of malignancy. These data suggest that Bcl-XL carries out anti-apoptotic functions instead of Bcl-2 during the development of oral squamous cell carcinoma, and may be valuable as the biomarker to inform the oral cancer progression.