Jung-Min Shin1, Dae-Kyoung Choi1, Hye-Young Kang2, Kyung-Cheol Sohn1, Young Lee1, Chang Deok Kim1, Jeung-Hoon Lee1, Byung Cheol Park3. 1. Department of Dermatology, School of Medicine, ChungNam National University Daejeon, Republic of Korea. 2. Department of Dermatology, Medical College, Dankook University, Cheonan, Republic of Korea. 3. Department of Dermatology, School of Medicine, ChungNam National University Daejeon, Republic of Korea; Department of Dermatology, Medical College, Dankook University, Cheonan, Republic of Korea. Electronic address: shinam73@hotmail.com.
Abstract
BACKGROUND: The exact physiological function of REIC/Dkk-3 in the development of squamous cell carcinoma(SCC) remains unclear. OBJECTIVE: We aimed to investigate the expression pattern and functional role of REIC/Dkk-3 in 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. 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. CONCLUSION: REIC/Dkk-3 could be involved early in SCC development and have inhibitory effect on the development of SCC.
BACKGROUND: The exact physiological function of REIC/Dkk-3 in the development of squamous cell carcinoma(SCC) remains unclear. OBJECTIVE: We aimed to investigate the expression pattern and functional role of REIC/Dkk-3 in 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 SCIDmice respectively, and tumor growth was evaluated. 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. CONCLUSION: REIC/Dkk-3 could be involved early in SCC development and have inhibitory effect on the development of SCC.