High levels of nm23-H1 and nm23-H2 messenger RNA in human squamous-cell lung carcinoma are associated with poor differentiation and advanced tumor stages.
Expression of the candidate metastasis-suppressor gene nm23-H1 has been shown to correlate inversely with metastatic potential in some human tumors, but not in all. Until now, few studies have been carried out on the activity of the homologous nm23-H2 gene in human cancer. No nm23 transcription studies exist for human lung cancer so far. To determine whether the nm23 genes could have a metastasis-suppressor function in non-small-cell lung carcinoma (NSCLC), pulmonary sarcoma and carcinoids, we analysed both nm23-HI and nm23-H2 mRNA levels in 37 tumor samples obtained from patients who underwent potentially curative resection between 1986 and 1990, and in 4 metastatic tumors obtained from autopsy. As compared to corresponding healthy lung parenchyma, both nm23-HI and nm23-H2 transcript levels were elevated in 37 of 41 tumors. The increases in nm23 mRNA expression were stronger in advanced stages of squamous-cell carcinoma, large-cell carcinoma, sarcoma and carcinoids than in early stages of the respective tumor types. Within stages I and II of squamous-cell carcinoma, significantly higher nm23 mRNA levels were found in poorly differentiated tumors than in moderately differentiated ones. Moreover, an inverse correlation between nm23 expression and disease-free survival of the patients was observed. In conclusion, our results indicate that the increased nm23 expression in the analysed tumors is not consistent with the proposed metastasis-suppressor function, but the 2 nm23 genes nevertheless may be implicated in the mechanism of tumor progression.
Institute of Human Genetics, University of Saar, Homburg/Saar, Germany.
M
M
Engel
B
B
Theisinger
T
T
Seib
G
G
Seitz
H
H
Huwer
K D
KD
Zang
C
C
Welter
S
S
Dooley
D000230:Adenocarcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D001483:Base Sequence; D002277:Carcinoma / Q000737:chemistry / Q000235:genetics / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D002454:Cell Differentiation; D015972:Gene Expression Regulation, Neoplastic; D016153:Genes, Suppressor; D006801:Humans; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D008207:Lymphatic Metastasis; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009367:Neoplasm Staging; D009701:Nucleoside-Diphosphate Kinase; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D012334:RNA, Neoplasm / Q000032:analysis*; D016019:Survival Analysis; D014157:Transcription Factors / Q000032:analysis* / Q000235:genetics
D054778:NM23 Nucleoside Diphosphate Kinases; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D014157:Transcription Factors; C517938:NME1 protein, human; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins