The expression pattern and functional role of REIC/Dkk-3 in the development of cutaneous squamous cell carcinoma

REIC/Dkk-3 在皮肤鳞状细胞癌发展中的表达模式和功能作用

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作者:Jung-Min Shin, Dae-Kyoung Choi, Hye-Young Kang, Kyung-Cheol Sohn, Young Lee, Chang Deok Kim, Jeung-Hoon Lee, Byung Cheol Park

Background

The exact physiological function of REIC/Dkk-3 in the development of squamous cell carcinoma(SCC) remains unclear.

Conclusion

REIC/Dkk-3 could be involved early in SCC development and have inhibitory effect on the development of SCC.

Methods

We stained normal skin, actinic keratosis (AK) and SCC tissue with REIC/Dkk-3. The proliferation and migration of SCC 12 over-expressed with REIC/Dkk-3 were observed. For in vivo study, SCC12 cells in PBS, SCC12 cells containing LacZ, and REIC/Dkk-3-transduced SCC 12 cells were injected intra-dermally into the left and right backside flanks of SCID mice respectively, and tumor growth was evaluated.

Objective

We aimed to investigate the expression pattern and functional role of REIC/Dkk-3 in the development of SCC.

Results

REIC/Dkk-3 staining was detected throughout the full epidermis in normal skin, focally positive in AK. Negative or very low stain of REIC/Dkk-3 was observed in SCC in situ, keratoacanthoma, and SCC. REIC/Dkk-3 mRNA level in SCC was very low compared with that in normal skin tissue. REIC/Dkk-3 significantly decreased the proliferation and migration of SCC12 cells comparing with control (p<0.05). Cyclin D1 and CDK4/6 expression was slightly lower and p21 was very higher in REIC/Dkk-3-overexpressed group than in the LacZ group. Fewer ITGA6 cells were found in the REIC/Dkk-3 overexpressed group than in the LacZ control (p<0.01). Mean tumor volume was smallest in the REIC/Dkk-3 overexpressed group (p<0.01) 21days after the intradermal injection of SCC12 cells.

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