Transcriptional repressor snail and progression of human hepatocellular carcinoma.
OBJECTIVE
Snail protein is a suppressive transcriptional factor of E-cadherin that mediates cell-to-cell adhesion, tumor progression, and metastases. We explored the expression and function of Snail and its family member Slug in human hepatocellular carcinoma (HCC) to identify its role in tumor progression.


RESULTS
Transfection of Snail cDNA in Li-7, endogenous E-cadherin-positive human HCC cells, selectively induced the loss of E-cadherin protein expression. We then investigated the expression of Snail and Slug mRNA in 43 human tissue samples of HCC. Using in situ hybridization, Snail mRNA was determined to dominantly express in HCC cells, but not in bile duct cells, blood vessels or infiltrating leukocytes. The mRNA of Snail and Slug were quantified using real-time reverse transcriptase-PCR, and correlations with E-cadherin expression and clinicopathological factors were investigated. Snail mRNA was overexpressed in 7 cases (16%) of HCC compared with adjacent noncancerous liver tissue. E-Cadherin protein expression determined in the same 43 cases by immunohistochemistry was significantly down-regulated in those cases with Snail mRNA overexpression (P = 0.04). The tumor and nontumor ratio of Snail mRNA independently correlated with tumor invasiveness (P = 0.04). However, Slug mRNA correlated with neither E-cadherin expression nor tumor invasiveness.


CONCLUSIONS
The data indicate that Snail both down-regulates E-cadherin expression and promotes the invasion in human HCC.
Sugimachi
Keishi
K
Departments of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Tanaka
Shinji
S
Kameyama
Toshifumi
T
Taguchi
Ken-ichi
K
Aishima
Shin-ichi
S
Shimada
Mitsuo
M
Sugimachi
Keizo
K
Tsuneyoshi
Masazumi
M
D000368:Aged; D001652:Bile Ducts / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007962:Leukocytes / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014018:Tissue Distribution; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection
D015820:Cadherins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D008164:Luminescent Proteins; D012333:RNA, Messenger; C000604407:SNAI1 protein, human; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D049452:Green Fluorescent Proteins