-Abstract-
The proto-oncogene bcl-2 confers a survival advantage to cells by blocking
programmed cell death (apoptosis). Overexpression of bcl-2 probably plays a role in
tumorigenesis, and the expression of the bcl-2 protein has been investigated in many
kinds of tumors. An increased expression of nitric oxide synthetase(NOS) has been
observed in human colon cancer cell lines as well as in human gynecological, breast,
and CNS tumors.
However, there have been only a few reports on the expression of bcl-2 and
NOS2 in oral white lesions and cancer. The aim of this study was to
investigate the relationship between the expression of Bcl-2 and NOS2 and
several pathological parameters such as histological types and layers. We reported
desregulation of bcl-2 and NOS2 expression during progression from oral
white lesion, lichen planus and leukoplakia to squamous cell carcinoma. The obtained
results were as follows:
1. Immunohistochemical analysis with monoclonal antibodies to bcl-2 oncoprotein and
NOS2 in formalin-fixed paraffin-embedded tissue sections revealed that
bcl-2 expression is restricted to the basal cell layer and NOS2 was
mild expressed only in subepithelial inflammatory cells in normal human mucosa.
There wasn't specific finding of those in lichen planus and leukoplakia.
2. Bcl-2 immunoreactivity in severe epithelial dysplasia or CIS occurs throughout the epithelium, NOS2 reactivity in most superficial layer were noted.
3. In well-differentiated squamous cell carcinomas, mostly bcl-2 was overexpressed. In
moderated and poor squamous cell carcinomas, the expression of NOS2
was increased and that of bcl-2 was decreased.
4. The immunoreactivity of bcl-2 was 12.5% of normal mucosa, 30% of leukoplakia, 44%
of lichen planus and 67% of carcinoma in situ. In carcinoma, those were 43%, 50%
and 67% according to differentiation, respectively.
5. The immunoreactivity of NOS2 was 25% of normal mucosa, 70% of
leukoplakia, 78% of lichen planus and 100% of carcinoma in situ and epithelial dysplasia. In carcinoma, those were higher in moderated(100%) and poor(83%) squamous cell carcinomas than in well differentiated
type(71%).
6. The expression of bcl-2 and NOS2 by western blot was increased
highly in lichen planus and leukoplakia.
Therefore, the expression of bcl-2 was increased in the white and precancerous
lesions and that was decreased by differentiation of carcinoma. However,
NOS2 immunoreactivity in carcinoma in situ was lower than those in
moderated and poor squamous cell. These findings suggest that the interaction of bcl-2
and NOS2 may be roled importantly in growth and development of
carcinoma.
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