Cyclin D1 expression and its possible regulation in chewing tobacco mediated oral squamous cell carcinoma progression.

OBJECTIVE: Proto-oncogene cyclin D1 is a G1 phase specific cell cycle regulator and known for its role in various cancers. The aim of the study was to understand oral cancer progression by observing the mRNA and protein expression of cyclin D1.

METHODS: Different oral tissue samples were selected as a model to study oral cancer progression. Those include healthy oral mucosa, premalignant lesions (Leukoplakia, Erythroplakia, Oral SubMucous Fibrosis) and oral cancer (OSCC) samples. Cyclin D1 mRNA and protein expression were detected by slot-blot and by immunohistochemical methods, respectively.

RESULTS: Premalignant lesions (PML) showed average 3-fold increase in the mRNA expression than normal oral mucosa (p = 0.001) whereas only 1.3-fold increase in mRNA has been observed in OSCC samples over the PML. On the other hand OSCC showed average 4-fold increase in mRNA expression than normal oral mucosa (p < 0.001). Cyclin D1 protein accumulation has been observed in 31.3% (16/51) of the OSCC samples whereas the normal oral mucosa and the PML showed no immunoreactivity. Oral cancer samples showing positive cyclin D1 immunoreactivity has increased from 15.0% (3/20) well differentiated SCC to 31.2% (5/16) moderately differentiated SCC to 53.3% (8/15) poorly differentiated SCC, found statistically significant (p = 0.05).

CONCLUSION: By observing the expression of cyclin D1 in different stages, we have noticed two major transitions that occur in normal oral mucosa that leads to oral cancer. The first transitional event transforms the normal oral mucosa to PML whereas the second transition drives the PML to OSCC. These findings give evidence that the first transition induces cyclin D1 mRNA with no detectable cyclin D1 protein. The induction of mRNA is maintained with increased cyclin D1 protein accumulation in the second transition.