Down-regulation of insulin-like growth factor binding protein-5 (IGFBP-5): novel marker for cervical carcinogenesis.
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.
Miyatake
Takashi
T
Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 1-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Ueda
Yutaka
Y
Nakashima
Ryuichi
R
Yoshino
Kiyoshi
K
Kimura
Toshihiro
T
Murata
Takuya
T
Nomura
Taisei
T
Fujita
Masami
M
Buzard
Gregory S
GS
Enomoto
Takayuki
T
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
D014408:Biomarkers, Tumor; D004279:DNA, Viral; D018975:Insulin-Like Growth Factor Binding Protein 5; D012333:RNA, Messenger