An attempt to isolate genes responsible for spontaneous and experimental metastasis in the mouse model.
Cancer develops and progresses as genetic alterations occur subsequently. Onset process of cancer has become well understood in some types of cancer, such as colorectal cancers. In this process, responsible alterations were identified in numbers of oncogenes such as k-ras, and tumor suppressor genes such as p53, as Vogelstein proposed earlier in the multistage carcinogenesis theory. In contrast, our understanding remains short to draw such an adequate diagram for the process during which cancer becomes more malignant, i.e., metastatic. To examine the molecular basis for this progression step, mouse metastasis models have been established where tumor cell lines are inoculated into mice and metastasize to specific organs. The model using B16 melanoma cells is one of the most developed. BL6 subline, one of the most metastatic, was obtained from F10 subline simply through six rounds of in vitro selection. Nonetheless, BL6 cells metastasize lungs much more heavily than F10 cells when injected subcutaneously. The difference in gene expression between the two sublines is considered rather small but relevant for spontaneous metastasis. We began our research by elaborating a method for the construction of subtracted cDNA libraries, and made it applicable to BL6 and F10 cells. As a result, we were able to isolate a couple of genes that were expressed differently between the two sublines. As might be expected, each of the genes appeared to play a role more or less in distinct aspects of spontaneous metastasis of B16 melanoma cells. Moreover, similar roles were expected for the genes in the process by which human melanoma cells metastasize.
Ito
A
A
Department of Pathology, Osaka University Medical School, Suita, Japan. aito@patho.med.osaka-u.ac.jp
Watabe
K
K
Koma
Y
Y
Kitamura
Y
Y
D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D018920:Coculture Techniques; D000072259:Connexin 26; D017630:Connexins / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D015723:Gene Library; D006801:Humans; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008954:Models, Biological; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000378:metabolism; D009374:Neoplasms, Experimental; D009687:Nuclear Proteins / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D016601:RNA-Binding Proteins; D020718:Ribonucleoproteins, Small Nucleolar / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D000094524:Gasdermins
D014408:Biomarkers, Tumor; D000072259:Connexin 26; D017630:Connexins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D010749:Phosphoprotein Phosphatases; D020033:Protein Isoforms; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D020718:Ribonucleoproteins, Small Nucleolar; C425469:GSDMC protein, human; D000094524:Gasdermins; C499062:NOP58 protein, human; C438198:Nol5 protein, mouse