title: Increased expression of the NME1 gene is associated with metastasis in epithelial ovarian cancer.
abstract: The genetic events involved in the development of metastases of epithelial ovarian cancer are largely unknown. One gene postulated to play a role in tumour metastasis suppression is NME1 (nm23-H1), and an inverse relationship between NME1 expression and metastatic potential has been observed for some solid tumours. In this study we have investigated the levels of mRNA expression of the 2 isoforms of the NME gene, NME1 and NME2. A maximum of 45 tumours samples from 33 patients were available for Northern blot analysis. We observed variable levels expression of NME1 and NME2 mRNA. The average level of NME1, but not NME2, mRNA expression was statistically higher in metastatic biopsies when compared with primary tumour biopsies. To examine the possible tumour suppressor gene role of NME1 in ovarian tumours, 76 patients were investigated by Southern blot analysis to determine the rate of allelic deletion. Allele loss at 5 other chromosome 17 loci (D17S5, TP53, NF1, D17S74, D17S4) was also evaluated for many of these 76 patients. Allele loss was observed in 22/30 (73%) informative patients at the NME1 locus. We also observed high rates of allele loss at the other loci evaluated. No correlations with clinical stage, histological subtype or patient survival were observed in either mRNA or DNA analyses. We have established that tumour progression in ovarian cancer is accompanied by over-expression of the NME1 gene; however, despite high rates of allele loss at the NME1 locus, the concept that NME1 may be a candidate tumour suppressor gene in ovarian cancer cannot be confirmed by this study.
authors.affiliation: Department of Obstetrics and Gynaecology, University of Sydney, NSW, Australia.
authors.forename: J A
authors.initials: JA
authors.lastname: Leary
authors.forename: J
authors.initials: J
authors.lastname: Kerr
authors.forename: G
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: C P
authors.initials: CP
authors.lastname: Doris
authors.forename: T
authors.initials: T
authors.lastname: Hurst
authors.forename: C R
authors.initials: CR
authors.lastname: Houghton
authors.forename: M L
authors.initials: ML
authors.lastname: Friedlander
mesh_terms: D001483:Base Sequence; D002872:Chromosome Deletion; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism*; D009701:Nucleoside-Diphosphate Kinase; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D014157:Transcription Factors; C517938:NME1 protein, human; C517940:NME2 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins