Epithelial to mesenchymal transition: expression of the regulators snail, slug, and twist in pancreatic cancer.
OBJECTIVE
Epithelial to mesenchymal transitions are vital for tumor growth and metastasis. Several inducers of epithelial to mesenchymal transition are transcription factors that repress E-cadherin expression, such as Snail, Slug, and Twist. In this study, we aimed to examine the expression of these transcription factors in pancreatic cancer.


METHODS
The expression of Snail, Slug, and Twist was detected by immunohistochemistry in tissue samples from patients with pancreatic ductal adenocarcinoma. Five human pancreatic cancer cell lines (AsPC-1, Capan-1, HPAF-2, MiaPaCa-2, and Panc-1) were analyzed by reverse transcription-PCR, real-time PCR, and Western blotting. An orthotopic nude mouse model of pancreatic cancer was applied for in vivo experiments.


RESULTS
Seventy-eight percent of human pancreatic cancer tissues showed an expression of Snail, and 50% of the patients displayed positive expression of Slug. Twist showed no or only weak expression. Snail expression was higher in undifferentiated cancer cell lines (MiaPaCa-2 and Panc-1) than in more differentiated cell lines (Capan-1, HPAF-2, AsPC-1). Expression of Slug was detected in all cell lines with different intensities. Twist was not expressed. After exposure to hypoxia, the Twist gene was activated in all five pancreatic cancer cell lines.


CONCLUSIONS
The transcription factors Snail and Slug are expressed in pancreatic cancer but not in normal tissue, suggesting a role in the progression of human pancreatic tumors. Twist, activated by hypoxia, may play an important role in the invasive behavior of pancreatic tumors.
Hotz
Birgit
B
Department of Surgery I, Charité-Medical School, Campus Benjamin Franklin, Berlin, Germany.
Arndt
Marco
M
Dullat
Sonja
S
Bhargava
Sarah
S
Buhr
Heinz-J
HJ
Hotz
Hubert G
HG
D015703:Antigens, CD / Q000032:analysis; D015820:Cadherins / Q000032:analysis; D015687:Cell Hypoxia; D004848:Epithelium / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008648:Mesoderm / Q000473:pathology*; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000032:analysis* / Q000502:physiology; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000032:analysis* / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000032:analysis* / Q000502:physiology
D015703:Antigens, CD; C050361:CDH2 protein, human; D015820:Cadherins; D009687:Nuclear Proteins; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; C103173:TWIST1 protein, human; D014157:Transcription Factors; D051879:Twist-Related Protein 1