Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas, intestinal metaplasia, and non-neoplastic gastric tissues.
Trefoil factor family (TFF) domain peptides consist of three members that play a role in intestinal mucosal defence and repair, and in tumourigenesis. The role of the three TFF members in the gastric carcinogenesis cascade remains poorly defined. This study examined seven gastric cell lines, 50 gastric cancers and their adjacent non-cancer tissues, and tissues from 40 non-cancer patients, in order to elucidate the chronology of TFF expression in various stages of gastric carcinogenesis. TFF expression was determined by RT-PCR, immunohistochemistry, and western blot. Aberrant expression of TFF1, TFF2, and TFF3 was frequently detected in gastric cell lines. Specifically, TFF1 was detected in all non-cancer patients, but was detected in only 50% of gastric cancer and 66% of adjacent normal tissues. TFF2 expression was demonstrated in 87.5% of non-cancer patients, 34% of gastric carcinomas, and 58% of adjacent non-cancer tissues. There was a significant correlation between TFF1 and TFF2 expression in gastric cancer and adjacent non-cancer tissues (p<0.001). By contrast, TFF3 was detected in 25% of non-cancer patients and showed a predilection for areas with intestinal metaplasia (p=0.005). Sixty-two per cent of gastric cancers and 24% of neighbouring non-cancer tissues showed TFF3 expression. Immunoreactivity against TFF3 was demonstrated in goblet cells of intestinal metaplasia and within the cytoplasm and nuclei of tumour cells. Progressive loss of TFF1 and TFF2, together with the induction of TFF3, is likely to be involved in the early stage of the multi-step gastric carcinogenesis pathway.
Leung
Wai K
WK
Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong. wkleung@cuhk.hk
Yu
Jun
J
Chan
Francis K L
FK
To
Ka F
KF
Chan
Michael W Y
MW
Ebert
M P A
MP
Ng
Enders K W
EK
Chung
S C Sydney
SC
Malfertheiner
Peter
P
Sung
Joseph J Y
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018450:Disease Progression; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D015870:Gene Expression; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008679:Metaplasia / Q000378:metabolism; D008875:Middle Aged; D009077:Mucins; D009124:Muscle Proteins; D009363:Neoplasm Proteins / Q000378:metabolism*; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011230:Precancerous Conditions / Q000378:metabolism* / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013270:Stomach / Q000473:pathology; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D006133:Growth Substances; D009077:Mucins; D009124:Muscle Proteins; D009363:Neoplasm Proteins; D009479:Neuropeptides; D010455:Peptides; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C051838:TFF1 protein, human; C000604007:TFF2 protein, human; C082495:TFF3 protein, human; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071163:Trefoil Factor-1; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D025521:Tumor Suppressor Proteins