title: Krüppel-like factors 4 and 5 expression and their involvement in differentiation of oral carcinomas.
abstract: Proliferation-differentiation balance of epithelial cells is regulated by Krüppel-like factors (KLF) 4 and 5, and the unbalanced expression relates to carcinoma progression. However, little is known about the expression and role in oral carcinomas. This study examined expression of KLF4 and KLF 5 in the carcinomas by immunohistochemistry (n = 67) and the involvement in proliferation and differentiation of carcinoma cells. KLF4 was detected in keratinizing carcinoma cells and KLF5 in non-keratinizing cells. KLF4 staining declined in the patient with lymph node metastasis (P < 0.05) and in parallel with the histological dedifferentiation (P = 0.09). Exogenous overexpression of KLF4 arranged cells in a cobble-like structure with desmosomes and KLF5 elongated cells like fibroblasts without desmosomes. KLF4 suppressed fibronectin expression, and KLF5 down-regulated and degraded E-cadherin. The proliferation was not affected by KLFs. Thus, down-regulation of KLF4 and up-regulation of KLF5 may stimulate oral carcinoma progression through the dedifferentiation of carcinoma cells.
authors.affiliation: Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University Fujimi 1-9-20, Chiyoda-ku, Tokyo 102-8159, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Shibata
authors.affiliation: Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University Fujimi 1-9-20, Chiyoda-ku, Tokyo 102-8159, Japan.
authors.forename: Tadashige
authors.initials: T
authors.lastname: Chiba
authors.affiliation: Department of Biology, School of Life Dentistry at Tokyo, The Nippon Dental University Fujimi 1-9-20, Chiyoda-ku, Tokyo 102-8159, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsuoka
authors.affiliation: Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University Fujimi 1-9-20, Chiyoda-ku, Tokyo 102-8159, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Mihara
authors.affiliation: Department of Oral Surgery, School of Medicine, Kanazawa University Takara-machi 13-1, Kanazawa, Ishikawa, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kawashiri
authors.affiliation: Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University Fujimi 1-9-20, Chiyoda-ku, Tokyo 102-8159, Japan.
authors.forename: Kazushi
authors.initials: K
authors.lastname: Imai
mesh_terms: D000368:Aged; D015820:Cadherins / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D054337:Cell Dedifferentiation / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D006801:Humans; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D015820:Cadherins; C000715467:KLF4 protein, human; C492214:KLF5 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors
keywords: Differentiation; KLF; oral carcinoma; progression