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Increased Lung Metastasis in Transgenic NM23-Null/SV40 Mice with Hepatocellular Carcinoma
- Source :
- JNCI: Journal of the National Cancer Institute. 97:836-845
- Publication Year :
- 2005
- Publisher :
- Oxford University Press (OUP), 2005.
-
Abstract
- Background: The metastasis-suppressing role of the NM23 gene in the metastatic spread of solid tumors is still debated. We examined the role of NM23 in tumor development and metastatic dissemination by using transgenic mice that lack mouse NM23 (NM23-M1) in two mouse models of hepatocellular carcinoma (HCC) that recapitulate all steps of tumor progression. Methods: We induced HCC in mice that contained (NM23-M1 +/+ ) or lacked (NM23-M1 − / − ) NM23-M1 by diethylnitrosamine injection or by a crossing scheme that transferred a transgene that leads to liver expression of simian virus 40 large T antigen (ASV mice). We used microscopic examination and immunohistochemistry to analyze tumor progression. Expression of Nm23 protein isoforms (Nm23-M1 and Nm23-M2) and several tumor markers was analyzed in the primary tumor and in metastases by Western blotting. The statistical signifi cance of differences in the incidence of Nm23-M2 overexpression in null mice relative to that in wild-type mice was tested by a one-sided Fisher’s exact test. The statistical signifi cance of differences in the incidence of metastases was examined using one-sided chisquare tests. All other statistical tests were two-sided. Results: In both models, Nm23-M1 and/or Nm23-M2 were overexpressed in the primary liver tumors compared with nontumor liver tissue; however, the lack of the NM23-M1 gene had no effect on primary tumor formation in either model. ASV mice developed pulmonary metastases that were positive for the Hep-Par 1 antibody, which recognizes a specifi c hepatocyte antigen, whereas the few pulmonary nodules that developed in diethylnitrosamine-injected mice were negative for this antigen. Statistically signifi cantly more ASV/NM23-M1 − / − mice than ASV/NM23-M1 +/+ mice developed lung metastases (69.2% versus 37.5%; difference = 31.7%, 95% confi dence interval = 13.1% to 50.3%; P
- Subjects :
- Genetically modified mouse
Cancer Research
Pathology
medicine.medical_specialty
Lung Neoplasms
Blotting, Western
Mice, Transgenic
Cyclin A
Simian virus 40
Biology
Gene Expression Regulation, Enzymologic
Metastasis
Mice
Liver Neoplasms, Experimental
Antigen
Antigens, Neoplasm
Biomarkers, Tumor
medicine
Animals
Diethylnitrosamine
Antigens, Viral, Tumor
Chi-Square Distribution
Incidence
Cancer
NM23 Nucleoside Diphosphate Kinases
medicine.disease
Immunohistochemistry
Primary tumor
Up-Regulation
Gene Expression Regulation, Neoplastic
Mice, Inbred C57BL
Liver
Oncology
Tumor progression
Nucleoside-Diphosphate Kinase
Hepatocellular carcinoma
Disease Progression
Subjects
Details
- ISSN :
- 14602105 and 00278874
- Volume :
- 97
- Database :
- OpenAIRE
- Journal :
- JNCI: Journal of the National Cancer Institute
- Accession number :
- edsair.doi.dedup.....91db9262fd68ab45143f71766d589b51