J Mol Histol. 42(6):499-504. 2011. doi: 10.1007/s10735-011-9357-z
Dickkopf (Dkk)-3 and β-catenin expressions increased in the transition from normal oral mucosal to oral squamous cell carcinoma.
Dickkopf (Dkk)-3, an inhibitor of the Wnt/β-catenin pathway, is reported as a potential tumor suppressor gene in many cancers. To gain a better comprehension of the mechanisms involved in the carcinogenesis of oral squamous epithelium, protein expression and localization of Dkk-3 and β-catenin was investigated in normal epithelium, dysplasias and squamous cell carcinoma (SCC). An increase in β-catenin and Ki-67 expressions was observed from dysplasias to poorly differentiated SCC. Interestingly, an increase in Dkk-3 positive cells was also noted, which was correlated to the cancer progression step. A change in Dkk-3 localization during the transformation of normal oral epithelium to SCC was clearly observed. Dkk-3 was localized in the cell membrane in normal oral epithelium and in dysplasias, whereas that was localized in both cell membrane and cytoplasm in SCC. These results suggest that Dkk-3 is involved in the carcinogenesis of SCC with a distinct function from those in other cancers.
What to examine：Does the protein expression of DKK3 alter in carcinogenesis step of oral mucosa?
Results：DKK3 protein expression increased according to the malignant transformation oral mucosa from precancerous
lesion to invasive carcinoma.
My colleagues and I firstly identified DKK3 gene as a candidate specific cancer-associated gene in HNSCC (Katase N et al. Oncol Res. 2008). For the next step, we investigated DKK3 protein expression in 1) HNSCC tissue samples and 2) oral precancerous lesions (i.e. epithelial dysplasia) and carcinoma in situ. The results of the former was reported as another article (Katase N et al. Oncol Lett. 2013）.Here, I describe the summary of the latter.
DKK3 expression and localization change in oral precancerous lesion, carcinoma in situ and invasive carcinoma.
In the normal oral mucosa, DKK3 expression was observed in the cell membrane of paranasal layer and prickle cell layer of squamous epithelia, and basal cell layer was negative for DKK3 (▲). However, in dysplastic epithelia, DKK3 positive area was increased and its localization changed into cytoplasmic. Cytoplasmic expression of DKK3 was also observed in basal layer.
These results revealed that DKK3 protein expression increases according to the malignant progression of oral muosa, with localization change from membranous to cytoplasmic.