title: The expression pattern and functional role of REIC/Dkk-3 in the development of cutaneous squamous cell carcinoma.
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.
  
  
  CONCLUSIONS
  REIC/Dkk-3 could be involved early in SCC development and have inhibitory effect on the development of SCC.
authors.affiliation: Department of Dermatology, School of Medicine, ChungNam National University Daejeon, Republic of Korea.
authors.forename: Jung-Min
authors.initials: JM
authors.lastname: Shin
authors.affiliation: Department of Dermatology, School of Medicine, ChungNam National University Daejeon, Republic of Korea.
authors.forename: Dae-Kyoung
authors.initials: DK
authors.lastname: Choi
authors.affiliation: Department of Dermatology, Medical College, Dankook University, Cheonan, Republic of Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Kang
authors.affiliation: Department of Dermatology, School of Medicine, ChungNam National University Daejeon, Republic of Korea.
authors.forename: Kyung-Cheol
authors.initials: KC
authors.lastname: Sohn
authors.affiliation: Department of Dermatology, School of Medicine, ChungNam National University Daejeon, Republic of Korea.
authors.forename: Young
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Dermatology, School of Medicine, ChungNam National University Daejeon, Republic of Korea.
authors.forename: Chang Deok
authors.initials: CD
authors.lastname: Kim
authors.affiliation: Department of Dermatology, School of Medicine, ChungNam National University Daejeon, Republic of Korea.
authors.forename: Jeung-Hoon
authors.initials: JH
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Byung Cheol
authors.initials: BC
authors.lastname: Park
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D063646:Carcinogenesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018925:Chemokines; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D055623:Keratosis, Actinic / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D014411:Neoplastic Stem Cells; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; C405061:Dkk3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins
keywords: Expression; Inhibition; REIC/Dkk-3; Squamous cell carcinoma