Reduced tumor incidence, metastatic potential, and cytokine responsiveness of nm23-transfected melanoma cells.
Reduced expression of the nm23 gene in certain rodent model systems and human breast tumors has been correlated with high tumor metastatic potential. To investigate the functional effects of nm23 expression, we have transfected a constitutive murine nm23-1 expression construct into highly metastatic K-1735 TK murine melanoma cells. TK clones expressing the exogenous nm23-1 construct exhibited a reduced incidence of primary tumor formation, significant reductions in tumor metastatic potential independent of tumor cell growth, and altered responses to the cytokine transforming growth factor beta 1 in soft agar colonization assays, compared with control-transfected TK clones. In contrast, nm23-1-transfected TK clones exhibited no significant differences in intrinsic tumor cell growth, i.e., primary tumor size in vivo, anchorage-dependent growth rate in vitro, and anchorage-independent colony formation in soft agar in vitro. The data demonstrate a suppressive effect of nm23 on several aspects of the cancer process, including tumor metastasis.
Leone
A
A
Laboratory of Pathology National Cancer Institute, of Health Bethesda, Maryland 20892.
Flatow
U
U
King
C R
CR
Sandeen
M A
MA
Margulies
I M
IM
Liotta
L A
LA
Steeg
P S
PS
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D004273:DNA, Neoplasm; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D008545:Melanoma; D051379:Mice; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D054778:NM23 Nucleoside Diphosphate Kinases; D009362:Neoplasm Metastasis / Q000235:genetics*; D009368:Neoplasm Transplantation; D009701:Nucleoside-Diphosphate Kinase; D010641:Phenotype; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D014157:Transcription Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D054778:NM23 Nucleoside Diphosphate Kinases; D011506:Proteins; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins