The clinical implication of 14-3-3 sigma expression in primary gastrointestinal malignancy.
14-3-3 Sigma is a checkpoint control gene that promotes G2 arrest following DNA damage. The inactivation of the 14-3-3 sigma gene, primarily by methylation-mediated silencing, has been reported in various human cancers. The loss of 14-3-3 sigma expression may contribute to malignant transformation by impairing the G2/M cell cycle checkpoint function, allowing an accumulation of genetic defects. In this report, we measured 14-3-3 sigma expression in 34 gastric and 35 colorectal cancers by using semi-quantitative reverse transcription-polymerase chain reaction and Western blot analysis. We also analyzed the association between 14-3-3 sigma expression and clinicopathological parameters including p53 status. Semi-quantitative reverse transcription-polymerase chain reaction and Western blot analysis showed that 14-3-3 sigma was significantly overexpressed in gastric and colorectal cancer tissues compared with normal ones (P<0.01). The immunoreactive 14-3-3 sigma protein was mainly detected in cytoplasm of cancer cells. Sigma overexpression tended to be associated with lymph node metastasis (P=0.08) in colorectal cancer. There was significant correlation between 14-3-3 sigma protein expression and the Ki-67 labeling index in gastric cancer (P=0.001). No significant association was observed between 14-3-3 sigma expression and p53 status. These results suggest that overexpressed 14-3-3 sigma in cancer cells might be induced by the p53 independent pathway, and that increased 14-3-3 sigma expression could contribute to cancer cell proliferation and the development and/or progression of human gastrointestinal cancers.
Tanaka
Kouji
K
The Second Department of Surgery, Mie University School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan.
Hatada
Tsuyoshi
T
Kobayashi
Minako
M
Mohri
Yasuhiko
Y
Tonouchi
Hitoshi
H
Miki
Chikao
C
Nobori
Tsutomu
T
Kusunoki
Masato
M
D048948:14-3-3 Proteins; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis*; D015153:Blotting, Western; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology*; D005092:Exonucleases / Q000032:analysis / Q000096:biosynthesis*; D005095:Exoribonucleases; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology*
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D005092:Exonucleases; D005095:Exoribonucleases; C413442:SFN protein, human