Expression of hepatocyte growth factor and c-met in ulcerative colitis.
OBJECTIVE
This study was designed to determine if the hepatocyte growth factor (HGF)-Met system is involved in the repair process of inflamed mucosa of ulcerative colitis (UC) and in the development of UC-associated colorectal cancer.


METHODS
HGF and c-met gene expressions were quantified in colonic mucosal specimens from healthy control subjects, patients with UC and patients with UC-associated colorectal cancer, using the competitive reverse transcription-polymerase chain reaction. Expression of HGF protein was determined by immunoblot analysis. Expression of c-Met protein was analyzed immunohistochemically.


RESULTS
HGF and c-met gene expressions were increased in inflamed mucosa of UC, compared with control subjects. Gene expression of HGF was also increased in the surrounding inflamed mucosa of UC-associated cancers. In cases in which the HGF gene expression was increased, an apparent increase in protein levels of HGF in inflamed mucosa of UC were observed by immunoblot analysis. The c-met gene was overexpressed in UC-associated cancers and a high level of immunoreactivity of the c-Met protein was immunohistochemically detected within the cancer cells.


CONCLUSIONS
We showed that HGF and c-met expression is increased in the inflamed mucosa of UC and that c-met is overexpressed in UC-associated colorectal cancers. These observations suggest HGF-Met system is involved in the repair process of the inflamed mucosa of UC and provide further support for the view that the inappropriate expressions of both HGF and c-met genes predispose to the development of colorectal cancer in patients with UC.
Kitamura
S
S
Department of Internal Medicine and Molecular Science, Graduate School of Medicine, Osaka University, Suita, Japan.
Kondo
S
S
Shinomura
Y
Y
Isozaki
K
K
Kanayama
S
S
Higashimoto
Y
Y
Minami
T
T
Kiyohara
T
T
Yasunaga
Y
Y
Ishikawa
H
H
Ohtani
T
T
Ishiguro
S
S
Matsuzawa
Y
Y
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000150:complications / Q000378:metabolism*; D003106:Colon / Q000737:chemistry; D003110:Colonic Neoplasms / Q000737:chemistry / Q000209:etiology; D005260:Female; D015870:Gene Expression; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D019859:Proto-Oncogene Proteins c-met / Q000032:analysis / Q000235:genetics*; D012004:Rectal Neoplasms / Q000737:chemistry / Q000209:etiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met