Snai2 expression enhances ultraviolet radiation-induced skin carcinogenesis.
Snai2, encoded by the SNAI2 gene, has been shown to modulate epithelial-mesenchymal transformation (EMT), the conversion of sessile epithelial cells attached to adjacent cells and to the basement membrane into dissociated and motile fibroblastic cells. EMT occurs during development, wound healing, and carcinoma progression. Using Snai2-null mice (Snai2(lacZ)), we evaluated the role of Snai2 in UV radiation (UVR)-induced skin carcinogenesis. In chronically UVR-exposed nontumor-bearing skin from Snai2-null mice, inflammation and epidermal proliferation were decreased compared with wild-type (+/+) skin. Snai2-null mice had a consistently lower tumor burden than +/+ mice. In addition, null mice developed fewer aggressive spindle cell tumors, believed to arise from squamous cell carcinomas that have undergone EMT, than +/+ mice; however, the difference in tumor type distribution between the two genotypes was not statistically significant. No metastases were observed in either the +/+ or Snai2-null mice. Using quantitative reverse transcriptase-polymerase chain reaction and immunohistochemistry, we showed that the spindle cell tumors in the Snai2-null mice demonstrated impaired EMT, as shown by decreased vimentin and increased cadherin 1 expression. This study confirms a role for Snai2 in EMT, but demonstrates that Snai2 expression is not required for the development or progression of UVR-induced skin tumors.
Newkirk
Kimberly M
KM
Department of Veterinary Biosciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43235, USA.
Parent
Allison E
AE
Fossey
Stacey L
SL
Choi
Changsun
C
Chandler
Heather L
HL
Rajala-Schultz
Päivi J
PJ
Kusewitt
Donna F
DF
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002471:Cell Transformation, Neoplastic; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009381:Neoplasms, Radiation-Induced / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D012878:Skin Neoplasms / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014466:Ultraviolet Rays / Q000009:adverse effects*
D015820:Cadherins; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors