title: Expression of keratinocyte growth factor receptor correlates with expansive growth and early stage of gastric cancer.
abstract: The keratinocyte growth factor receptor, also known as KGFR/FGFR2 IIIb, is mainly localized in epithelial cells, and participates in the proliferation of these cells. In contrast, a recent study has revealed that the overexpression of KGFR in salivary adenocarcinoma induces growth inhibition, cell differentiation and apoptosis. We attempted to clarify the expression and role of KGFR in normal and cancerous human gastric tissues and cancer cell lines. Reverse-transcription polymerase chain reaction and Western blot analyses showed KGFR mRNA and its protein expression in NUGC-4, KATO-III and MKN-7 gastric cancer cell lines, but not in the NS-8 cell line. Immunohistochemically, KGFR immunoreactivity was weakly detected in the luminal surface of normal gastric epithelial cells. In addition, KGFR immunoreactivity was strongly detected in the nucleus and cytoplasm of many parietal cells. In gastric cancer tissue, KGFR was expressed in the cell membrane and cytoplasm of cancer cells in 46 of 126 (36.5%) cases. KGFR expression in gastric cancer cells was significantly associated with early-type macroscopic findings, shallow invasion of the gastric wall and expansive growth type. KGFR expression tended to correlate with a good prognosis in gastric cancer. These findings indicate that KGFR expression plays important roles in the differentiation of normal gastric epithelial cells and parietal cell functions. Furthermore, a decreased expression level or the non-expression of KGFR in gastric cancer cells may be associated with the proliferation and invasion of gastric cancer cells and a poor prognosis for the patient.
authors.affiliation: Department of Integrative Pathology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matsunobu
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Ishiwata
authors.forename: Masanori
authors.initials: M
authors.lastname: Yoshino
authors.forename: Masanori
authors.initials: M
authors.lastname: Watanabe
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Kudo
authors.forename: Koshi
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Akira
authors.initials: A
authors.lastname: Tokunaga
authors.forename: Takashi
authors.initials: T
authors.lastname: Tajiri
authors.forename: Zenya
authors.initials: Z
authors.lastname: Naito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010295:Parietal Cells, Gastric / Q000378:metabolism; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D012333:RNA, Messenger; D051497:Receptor, Fibroblast Growth Factor, Type 2; C065104:keratinocyte growth factor receptor