title: Down-regulation of insulin-like growth factor binding protein-5 (IGFBP-5): novel marker for cervical carcinogenesis.
abstract: To better understand the underlying pathways of cervical carcinogenesis, cDNA microarray analysis was performed on 2 sets of squamous cell carcinomas (SCCs) and their adjacent normal squamous epithelia. Consistently altered expression was detected for 32 genes. Real-time RT-PCR analysis was conducted on a selected subset of these genes (S100A2, GPC4, p72, IGFBP-5, TRIM2 and NAB2) for 14 additional SCCs and 10 normal epithelia. This found that, of the 6 candidate genes, only the insulin-like growth factor binding protein-5 (IGFBP-5) mRNA was generally and significantly under-expressed in SCCs (p < 0.001). All normal cervical epithelia (30 of 30) stained positively for IGFBP-5 protein, with 70% showing strong staining, whereas 65% (17/26) of SCC had complete loss of IGFBP-5, and only 8% (2/26) SCC retained strong expression (p < 0.001). Immunohistochemistry of premalignant cervical intraepithelial neoplasia (CIN) lesions shows a significantly weaker or negative staining in advanced CIN3 lesions compared with normal squamous epithelia (p = 0.001). This is the first study to show that down-regulation of IGFBP-5 protein correlates with cervical carcinogenesis and does so at a preneoplastic stage.
authors.affiliation: Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 1-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Miyatake
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Ueda
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Nakashima
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshino
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Kimura
authors.forename: Takuya
authors.initials: T
authors.lastname: Murata
authors.forename: Taisei
authors.initials: T
authors.lastname: Nomura
authors.forename: Masami
authors.initials: M
authors.lastname: Fujita
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Buzard
authors.forename: Takayuki
authors.initials: T
authors.lastname: Enomoto
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology; D004279:DNA, Viral / Q000032:analysis; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D052162:Human papillomavirus 16 / Q000145:classification / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D004279:DNA, Viral; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger