title: Gene expression changes in progression of cervical neoplasia revealed by microarray analysis of cervical neoplastic keratinocytes.
abstract: To evaluate the gene expression changes involved in neoplastic progression of cervical intraepithelial neoplasia. Using microarray analysis, large-scale gene expression profile was carried out on HPV16-CIN2, HPV16-CIN3, and normal cervical keratinocytes derived from two HPV16-CIN2, two HPV-CIN3 lesions, and two corresponding normal cervical tissues, respectively. Differentially expressed genes were analyzed in normal cervical keratinocytes compared with HPV16-CIN2 keratinocytes and in HPV16-CIN2 keratinocytes compared with HPV16-CIN3 keratinocytes; 37 candidate genes with continuously increasing or decreasing expression during CIN progression were identified. One of these genes, phosphoglycerate dehydrogenase, was chosen for further characterization. Quantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis confirmed that expression of phosphoglycerate dehydrogenase consistently increases during progression of CIN toward cancer. Gene expression changes occurring during CIN progression were investigated using microarray analysis, for the first time, in CIN2 and CIN3 keratinocytes naturally infected with HPV16. Phosphoglycerate dehydrogenase is likely to be associated with tumorigenesis and may be a potential prognostic marker for CIN progression.
authors.affiliation: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, via Fossato di Mortara 64/B, Ferrara, Italy.
authors.forename: John Charles
authors.initials: JC
authors.lastname: Rotondo
authors.forename: Silvia
authors.initials: S
authors.lastname: Bosi
authors.forename: Cristian
authors.initials: C
authors.lastname: Bassi
authors.forename: Manuela
authors.initials: M
authors.lastname: Ferracin
authors.forename: Giovanni
authors.initials: G
authors.lastname: Lanza
authors.forename: Roberta
authors.initials: R
authors.lastname: Gafà
authors.forename: Eros
authors.initials: E
authors.lastname: Magri
authors.forename: Rita
authors.initials: R
authors.lastname: Selvatici
authors.forename: Stefania
authors.initials: S
authors.lastname: Torresani
authors.forename: Roberto
authors.initials: R
authors.lastname: Marci
authors.forename: Paola
authors.initials: P
authors.lastname: Garutti
authors.forename: Massimo
authors.initials: M
authors.lastname: Negrini
authors.forename: Mauro
authors.initials: M
authors.lastname: Tognon
authors.forename: Fernanda
authors.initials: F
authors.lastname: Martini
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D052162:Human papillomavirus 16 / Q000302:isolation & purification; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics; D050543:Phosphoglycerate Dehydrogenase / Q000235:genetics / Q000378:metabolism; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D050543:Phosphoglycerate Dehydrogenase