Overexpression of nm23-H1 and nm23-H2 genes in colorectal carcinomas and loss of nm23-H1 expression in advanced tumour stages.
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.
INSERM U 402, Faculté de Médecine, Hôpital Saint-Antoine, Paris, France.
J A
JA
Martinez
S
S
Prevot
B
B
Nordlinger
T M
TM
Nguyen
Y
Y
Lacarriere
A
A
Munier
I
I
Lascu
J C
JC
Vaillant
J
J
Capeau
M L
ML
Lacombe
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis*
D054778:NM23 Nucleoside Diphosphate Kinases; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins