Expression of fibroblast growth factor receptor 2 IIIc in human uterine cervical intraepithelial neoplasia and cervical cancer.
Fibroblast growth factor receptors (FGFRs) 1-3 have IIIb and IIIc isoforms, and we reported that FGFR2 IIIb is highly expressed in cervical keratinizing squamous cell carcinoma (SCC). In this study, we determined the expression and roles of FGFR2 IIIc in cervical intraepithelial neoplasia (CIN) and cervical cancer. In CINs 1 and 2, FGFR2 IIIc was found to be localized at the basal to lower two-thirds of the squamous epithelium, whereas it was localized in most of the squamous epithelium, except for the superficial layer in CIN 3. In situ hybridization (ISH) analysis showed that the expression patterns of FGFR2 IIIc mRNA are similar to those of FGFR2 IIIc protein in CINs. The FGFR2 IIIc protein was detected in all invasive cervical cancer patients (29 cases) and its mRNA was found to be strongly expressed in the invasive front of cancer cell nests. FGFR2 IIIc cDNA was stably transfected into CaSki cells, which are derived from a cervical SCC. The growth rates of the CaSki cells were higher than those of Mock cells in vitro, and the CaSki cells tended to form larger subcutaneous tumors in nude mice. These findings suggest that FGFR2 IIIc plays important roles in carcinogenesis and growth of cervical cancer cells. Anti-FGFR2 IIIc therapies may represent therapeutic strategies for inhibiting the growth of CIN and cervical cancer.
Kawase
Rieko
R
Department of Pathology, Integrative Oncological Pathology, Nippon Medical School, Tokyo 113-8602, Japan.
Ishiwata
Toshiyuki
T
Matsuda
Yoko
Y
Onda
Munehiko
M
Kudo
Mitsuhiro
M
Takeshita
Toshiyuki
T
Naito
Zenya
Z
D000328:Adult; D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D051497:Receptor, Fibroblast Growth Factor, Type 2