Increased expression of survivin in gastric cancer patients and in first degree relatives.
Survivin was recently described as an apoptosis inhibitor. Its pathogenic role in gastric cancer is largely unknown. Expression of survivin in gastric cancer and non-cancer first-degree relatives, and its association with apoptosis and cyclo-oxygenase-2 expression was investigated. Fifty gastric cancer, 30 non-cancer first-degree relatives, 20 normal controls and five gastric cancer cell lines were studied. Survivin and cyclo-oxygenase-2 were evaluated by reverse transcriptase-polymerase chain reaction, immunohistochemistry and Western blot. Survivin expression was absent from normal gastric mucosa. All five cancer cell lines and 34 out of 50 (68%) human gastric cancer tissues expressed survivin mRNA. Survivin expression was less frequent (22%; P<0.001) in adjacent non-tumour gastric tissues. Immunohistochemistry and Western blot obtained similar findings. Gastric cancers with survivin expression displayed significantly reduced apoptosis (P=0.02), and associated with cyclo-oxygenase-2 overexpression at both mRNA (P=0.001) and protein levels (P=0.041). Moreover, survivin mRNA was detected in the gastric mucosa of eight (27%) non-cancer relatives. Expression in non-cancer patients showed positive correlation with H. pylori infection (P=0.004). This demonstrates the frequent expression of survivin in gastric cancer and in first-degree relatives. Co-expression of survivin and cyclo-oxygenase-2 may suggest multiple pathways contributing to the inhibition of apoptosis in gastric cancer.
Yu
J
J
Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Leung
W K
WK
Ebert
M P A
MP
Ng
E K W
EK
Go
M Y Y
MY
Wang
H B
HB
Chung
S C S
SC
Malfertheiner
P
P
Sung
J J Y
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D015153:Blotting, Western; D002868:Chromosomal Proteins, Non-Histone / Q000096:biosynthesis*; D051546:Cyclooxygenase 2; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins; D010375:Pedigree; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D000077022:Survivin; D014407:Tumor Cells, Cultured
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases