Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages.

Abstract

Although a reduced expression of nm23 has been shown to correlate with a high metastatic potential in some human cancers, in colorectal cancers, conflicting data have been reported. As there are two homologous genes, nm23-H1 and nm23-H2, which encode the A and B subunits of nucleoside diphosphate kinase, efficient and simplified techniques were designed to selectively study nm23-H1 and -H2 expression in 35 colorectal cancers at both the protein and mRNA levels by immunoblotting, immunohistochemistry, and reverse transcription polymerase chain reaction (RT PCR) using specific antibodies and primers. Nm23-H1 and Nm23-H2 proteins were overexpressed in tumours compared with adjacent mucosa. This overexpression was lost, however, in some advanced cases: 89% and 81% of TNM (tumour, node, metastases) stages 0-II showed Nm23-H1 and -H2 overexpression, respectively, which significantly differed from 47% and 38% of stage III-IV tumours. Similar results were seen with nm23-H1 mRNA. Heterogenous labelling of tumoral cells was seen by immunohistological staining. This suggests a dichotomy: an overexpression of nm23-H1 and -H2 linked to early stages of cancer and a loss of nm23-H1 overexpression seen in more advanced stages. Therefore specific nm23-H1 determination should be evaluated as a prognostic factor in human colorectal carcinoma.

• Authors: J A Martinez, S Prevot, B Nordlinger, T M Nguyen, Y Lacarriere, A Munier, I Lascu, J C Vaillant, J Capeau, M L Lacombe
• Journal: Gut (Gut) Vol. 37 Issue 5 Pg. 712-20 (Nov 1995) ISSN: 0017-5749 [Print] England
• PMID: 8549951 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NM23 Nucleoside Diphosphate Kinases
• Transcription Factors
• NME1 protein, human
• Nucleoside-Diphosphate Kinase
• Monomeric GTP-Binding Proteins

Topics

• Adenocarcinoma (genetics, pathology)
• Adult
• Aged
• Aged, 80 and over
• Base Sequence
• Colorectal Neoplasms (genetics, pathology)
• Female
• Gene Expression
• Humans
• Immunohistochemistry
• In Vitro Techniques
• Liver Neoplasms (genetics, secondary)
• Male
• Middle Aged
• Molecular Sequence Data
• Monomeric GTP-Binding Proteins
• NM23 Nucleoside Diphosphate Kinases
• Neoplasm Staging
• Nucleoside-Diphosphate Kinase (analysis)
• Transcription Factors (analysis)